Isaac's tears are replaced with a charged blood laser beam. The beam is piercing and spectral, dealing damage to all enemies and ignoring all obstacles in its path.
The laser deals damage equal to Isaac's damage and deals damage each tick.
These ticks occur every 1/15th of a second (once every 4 frames). However, after the first damage tick, there is an additional pause for ~0.12 seconds (7 frames). Damage ticks work normally after that.
Brimstone ticks 13 times over the course of 0.9 seconds (54 frames).
Brimstone ticks 9 times over the course of ~0.63 seconds (38 frames).
Starting from 15.00 fire rate, the beam can last indefinitely as long as the fire key is held, and higher fire rate results in higher damage and larger scale.
Azazel starts the game with a short-ranged, slower-charging version of Brimstone. Without the long-range version, his mini-brimstone won't have enough length to use any homing items.
His Brimstone's shorter range can be increased with range-increasing items or pills.
Multi-shot effects like 20/20 will increase the number of beams accordingly, with exceptions listed below.
Although extremely unlikely, Isaac can shoot a total of 16 blood beams at a time via multi-shot items. If the number of blood beams would exceed this number, the beams' span will instead widen.
Tainted Azazel has a full-range, but thinner beam whose damage is halved unless enemies are cursed by his inherent Hemoptysis sneeze.
The beam will apply Tear effects and does so frequently thanks to its high tick rate.
Any item that grants homing tears: will cause the beam to make sharp turns and even loops to hit enemies, which is extremely powerful. Azazel's mini-brimstone does not home unless he has a high range stat.
Despite the fire rate penalty caused by The Inner Eye and Mutant Spider, the overall DPS increase is more significant compared to 20/20. However, if combined, 20/20 negates the fire rate penalty of the aforementioned items, which results in enormous damage output.
Almond Milk: Fires automatically upon reaching full charge. The beam lasts indefinitely as long as the fire key is held. The beam can change its direction while being fired, and can be aimed in any direction with joystick controls. The beam will also gain random worm trinket effects.
Increasing the tears stat will increase the damage and width of Brimstone as well.
Damage per Tick = (Damage × Fire Rate) ÷ 5
Azazel / Tainted Azazel: Picking up Brimstone with him will give him the regular version.
Apple! / Euthanasia / Tough Love: The beam can gain the damage multiplier from each of the items, although there is no visual difference. The bonus applies for the whole beam and not on a per-tick basis. Euthanasia loses its instant kill ability, however.
The bonus applies randomly on every tick of the beam, including the insta-kill ability from Euthanasia.
Anti-Gravity: An orb of energy expands, then shrinks while firing the beam after a delay. The orb still hurts enemies if they touch it. Isaac can start charging a new shot immediately after releasing the fire key without canceling the first shot, effectively allowing for a faster firing rate. It makes it harder to hit enemies with Azazel as the beam does not increase in range. Size and damage of the beams no longer scales with fire rate, nor is it possible to sustain a perpetual beam at above 15 fire rate.
Anti-Gravity + Soy Milk / Almond Milk: Allows auto-firing upon full charge, but without permanent beam uptime.
Anti-Gravity + Incubus: Isaac will fire Brimstone orbs, while Incubus will fire regular Brimstone beams.
Both Isaac and Incubus fire Brimstone orbs.
Brain Worm: The beam will curve 90 degrees in order to attack opponents, effectively acting as a stronger form of homing. Very strong against multi-segment bosses such as Pin or Mother.
Brimstone:
Additional copies of this item, such as from Diplopia / Crooked Penny, adds another beam, with no increase in charge time.
Additional copies of this item grant 1.2× damage multiplier and +1 damage and doubles the beam's width. Any further Brimstone only grants +1 damage.
If combined with Azazel's Birthright effect, the laser beam will be 4× wider.
The bigger beam granted by double Brimstone synergizes with other items as expected.
Chocolate Milk: Brimstone laser takes longer to fully charge, but can be released at any point. Width and damage of the laser increases with charge, from 25% damage and 50% width at minimum charge to 250% damage and 160% width at maximum charge.
Continuum: Brimstone laser travels through the wall and appears out the other side once.
Cricket's Body: Spawns split tears on the first enemy or obstacle the beam hits.
C Section: Shoots 4 fetus tears along with the Brimstone beam.
C Section + Soy Milk / Almond Milk: Small fetuses fire continuously alongside the beam.
The Ludovico Technique: Fetus tears no longer fire with the Brimstone circle, even on doing damage.
Dead Eye: The damage multiplier that was gained before picking up Brimstone will now be permanent. However, saving and quitting the run will result in this damage multiplier being permanently lost (which is a bug).
Dataminer: Dataminer can be used to underflow Isaac's tears to immediately bring it to 120, maxing out Brimstone's width and damage via tears.
Epic Fetus: Adds a Brimstone Sad Bombs effect: missile explosions shoot ten beams in all directions, massively increasing damage and area of effect.
Explosivo / Sinus Infection: The beam has a chance to stick tears to enemies on every other tick.
Eye of the Occult: Creates a controllable crosshair similar to Marked. Fires automatically upon reaching full charge. The beam curves towards the crosshair and then attempts to hit the wall Isaac is facing.
Brimstone + Tech.5 / Technology 2: Tech.5 and Technology 2 lasers are also affected by the crosshair but cannot create the crosshair on their own.
Guppy: Blue Flies are spawned at a rate of approximately one blue fly per tick (every other tick) of damage for each enemy it hits, up to 13 flies. The spawned blue flies will also move to attack the targeted enemy immediately.
Haemolacria: +20 Tear Delay after Haemolacria's tears down. Tears burst into 4-7 Brimstone beams that do Isaac's damage per tick.
Azazel / Tainted Azazel: Overrides these characters' Brimstone. Tears do not burst into Brimstone beams.
Double Brimstone: Grants +1 Damage but not the 1.2× damage multiplier. The width of the beams doubles.
Haemolacria + Chocolate Milk: The Brimstone beams deal full damage regardless of charge.
Haemolacria + Technology: The lasers coil the beams. This is purely visual and does not grant a 1.5× damage multiplier.
Head of the Keeper: Makes the laser yellow and each tick has a chance to drop a coin.
Hemoptysis: Enemies hit by the sneeze will gain a curse that increases the damage Brimstone deals to 2× and +3 flat damage. Enemies who die to Brimstone under the curse will damage and spread the curse to nearby enemies.
Holy Light: Every tick of the beam has a chance of summoning a beam of light.
Hook Worm: Beam shifts left to right while firing straight and forms angles that constantly flatten and expand, effectively increasing its width.
Jacob's Ladder: Upon hitting an enemy, wall, or obstacle, the beam generates sparks that home in on enemies.
Lead Pencil: Lead Pencil triggers approximately every 2 seconds as the beam is fired (charge time is not counted).
Loki's Horns: Adds a chance to shoot a beam from all four cardinal directions, similarly to Head of Krampus's effect.
Lost Contact: Beam destroys projectiles, although only during its damage tick interval. The projectiles are not instantly destroyed when they touch the beam.
The Ludovico Technique: The Ludovico Technique has priority. The beam forms a large ring that is controllable and does not need to be charged. The damage is dealt 15 times per second, unaffected by Tears. Enemies inside the ring without touching it are not hurt.
The Ludovico Technique + multi-shot effect: No effect.
The Ludovico Technique + C Section: Disables C Section. Fetuses no longer spawn.
Incubus' Brimstone laser is not affected by Ludovico Technique.
Adds a smaller controllable laser ring in addition to the main one.
The Ludovico Technique + A Lump of Coal: The ring increases in diameter when Isaac is further; 100% when he is on the center, 1.25× when he is 12.5 tiles of distance away.
The damage increases with distance but is reduced while Isaac is in the ring.
The damage increases 20% per tile of distance.
The Ludovico Technique + Mom's Knife: Overrides Brimstone.
The Ludovico Technique + Proptosis: The ring deals 1.5× Isaac's Damage at its largest, and 50% at its smallest. The ring increases in diameter when Isaac is closer; 1.25× when he is on the center, 100% when he is 12.5 tiles of distance away.
A Lump of Coal: The beam gradually increases in size and damage the farther it travels, with the damage increasing on a multiplier that is +20% per tile of distance. This allows for a huge damage increase from longer distances.
Marked: Fires automatically upon reaching full charge. Fires at the direction of the crosshair.
Mom's Eye: Adds a chance to shoot a beam from the back of Isaac's head.
Mom's Knife: Mom's Knife has priority. Does not apply Brimstone's tears down. Adds a small barrage of knives after the main knife is fired, with each knife doing 80% of / 2× Isaac's tear damage.
The barrage of knives goes all the way across the screen and does not return.
Charge amount increases the barrage size; 2-4 knives at 0%, 8-10 knives 100%.
This effect does not work with Azazel or Tainted Azazel's versions of Brimstone.
Mom's Wig: Holding down a fire button to charge the attack very rapidly rolls the probability to spawn blue spiders; releasing to fire the beam, however, does not.
The blue spiders only spawn while the beam is firing.
Monstro's Lung: Brimstone has priority. Does not apply Monstro's Lung's tears down. Fires 3-5 additional beams in random directions around Isaac. This effect also applies to Azazel and Tainted Azazel's Brimstone.
Charging a new Brimstone beam removes the original from in front of Isaac, but not the additional ones added by Monstro's Lung.
Multidimensional Baby: If a brimstone laser is shot through the baby, it will double the laser.
My Reflection: Makes the beam curve when moving. It has the same effect on Azazel's mini-brimstone but doubles the range.
Makes the beam shoot from the back. An oval beam is shot from the front instead.
Mucormycosis: The beam has 25% chance to spawn spore to enemies on every other tick.
Mysterious Liquid: Leaves a creep for each enemy and obstacle the beam hits, on every other tick. Azazel's Brimstone leaves creeps at the end of its range.
Ocular Rift: Rifts may appear where the beam hits rocks, walls, or enemies.
Ouroboros Worm: The beam will make large loops on itself. The homing is present, but unreliable.
The Parasite: Spawns two perpendicular beams on the first enemy or obstacle the beam hits.
Rotten Tomato: Each tick of the beam's damage can mark enemies.
Rubber Cement: Beams bounce off of walls once, creating a second beam that deals half/full damage.
If Azazel's mini Brimstone beam bounces off a wall, it effectively becomes a full-length Brimstone beam, but it will still only deal half damage.
Azazel's Brimstone no longer becomes a full length beam after bouncing, instead bouncing as a regular mini-Brimstone.
Soy Milk: The Brimstone beam bounces off the wall at a perpendicular angle to where the beam was fired.
Sad Bombs: Upon exploding, bombs release ten beams in all directions.
Brimstone does not benefit from Sad Bombs' flat damage bonus.
Soy Milk: Fires automatically upon reaching full charge. The beam lasts indefinitely as long as the fire key is held. The beam can change its direction while being fired, and can be aimed in any direction with joystick controls.
Increasing tears will also increase damage.
Damage per Tick = Damage × Fire Rate / 5
Soy Milk + Chocolate Milk: The beam does 25% more damage. Does not increase Isaac's damage stat itself.
Strange Attractor: Enemies are attracted towards the beam, improving its consistency. Consumables will also be moved by the beam.
Sulfur: Grants a larger beam with a 1.2× damage multiplier and +1 damage (same effect as picking up a second Brimstone).
Sulfuric Acid / Terra: The beam has a chance to destroy rocks every tick. The laser will not destroy sealed doors or open secret rooms.
Tammy's Head: Shoots ten beams in all directions. Given the item's single room charge, this makes for an extremely powerful synergy.
Brimstone does not benefit from Tammy's Head's flat damage bonus.
Tech.5: Tech.5 fires normally while charging Brimstone.
Technology: The Technology laser coils around the Brimstone beam, granting a 1.5x damage multiplier (it stacks with other similar multipliers like Cricket's Head or Magic Mushroom).
Technology's damage multiplier will be overridden if Isaac has the powered up version (from picking up Brimstone twice or using Sulfur with Brimstone); this can decrease Isaac's damage.
Technology 2: Both fire normally; the Technology laser fires while charging Brimstone.
Tech X: Tech X has priority. Does not apply Brimstone's tears down. Fires a Brimstone ring. This Brimstone ring is larger than the laser ring and has a much wider hitbox.
Double Brimstone: Further increases the width of the ring, and grants +1 Damage.
Tech X + Homing Shots: The ring bends itself to hit enemies if they are nearby.
Tech X + Mom's Knife: Mom's Knife and a Mom's Knife + Brimstone barrage are shot alongside the rings.
Tech X + Technology: The 1.5× damage multiplier from Brimstone + Technology is lost, but the laser fires while charging the Brimstone ring.
Fires a Brimstone ring coiled by a laser. The 1.5× damage multiplier from Brimstone + Technology is retained.
Tiny Planet: The beam will wrap around Isaac once and then shoot straight forward.
Tiny Planet + My Reflection: The beam will first wrap around Isaac, form an oval beam in a longer range, then shoot backward. Interestingly enough, the beam will look like a G clef symbol.
Uranus: The beam will freeze any enemies killed by it, so long as they are not immune to the freeze effect.
Wiggle Worm: Beam becomes wavy while firing straight, effectively increasing its width.
Epiphora: Effect only activates when holding charge in a specific direction, and deactivates when the charge is released, effectively making Epiphora useless unless Isaac has exceedingly high tear delay.
Fire Mind: The beam will not cause explosions, but will still set enemies on fire.
The Forgotten: The charged attack will spawn a Brimstone ball that will float in front of The Forgotten for a few seconds before disappearing. The Forgotten will still melee attack while performing this action.
Ghost Pepper: The flames can still shoot from Isaac while holding the fire button.
Has a chance to shoot flames for every other tick while the beam is being fired.
Godhead: Homing and stat bonuses apply, but the beam does not have a damaging aura.
Ipecac: Does not apply Ipecac's stat changes. The beam poisons enemies.
Isaac shoots Ipecac tears while charging Brimstone. Stat changes from both items are applied as normal, meaning that Ipecac fires slower and Brimstone charges slower, but Brimstone deals drastically increased damage.
Applies +2 flat damage, instead of Ipecac's damage up. Does not apply Ipecac's tears down. The beam explodes on the first enemy or obstacle it hits every other tick, dealing 10 + twice of Isaac's Damage. The beam gains a poison effect. The explosions do not occur when the beam narrows, meaning that they occur only twice per shot without Soy Milk / Almond Milk. The beam and its explosions poison enemies. The Ladder, when placed, will trigger the Ipecac-Brimstone explosions. (possibly a bug)
Ipecac + Haemolacria: The flat damage bonus is +40 instead of +2. Tears will explode into multiple brimstone beams, each of which explodes and has a chance to hit Isaac.
Isaac's Tears: Fires normal tears, but nearly instantly charges when charging Brimstone.
Fires normal tears. Charges at the same rate as Isaac's fire rate while charging Brimstone.
Fires normal tears. Charges when firing Brimstone.
Lachryphagy: Brimstone's range is lowered, but Lachryphagy tears will form at the end of the beam, which can be fed.
Large Zit: Creep shots will still be fired occasionally while holding the fire button.
Lodestone: Changes the beam to gray, can still apply the magnetized effect. The beams are not attracted to enemies with the magnetized effect.
Number One: Although Number One is otherwise purely beneficial with standard Brimstone, Azazel's range is severely affected.
Playdough Cookie: Brimstone will start cycling through colors and applies the standard chance of tear-effect on hit, with the homing effect occurring intermittently.
Pop!: Brimstone has shorter range, a bit longer than the default range of Azazel's mini-Brimstone, and it is not affected by Range. The beam fires Pop! tears at the end, which are Piercing.
The beam deals 2× Isaac's Damage, which is already doubled from the item's effect, at point blank-range. The damage quickly drops further along the beam, at about 0.8× per tile of distance.
The beam deals 6× Isaac's Damage at point-blank range. Decreases 13.3% of the damage per tile of distance, to the minimum of 0.1 point of damage at 7.5 tiles of distance.
Tainted Samson: Greatly decreases attack speed for Samson's rage mode melee attack and replaces the thrown jawbone with a large laser sphere (similarly to The Forgotten).
Brimstone's costume when powered-up by duplication
Azazel's version.
The Ludovico Technique with Brimstone.
Tiny Planet with Brimstone as Azazel.
Brimstone with Tiny Planet, Common Cold and Tammy's Head.
The Ludovico Technique with Brimstone and Wiggle Worm.
Brimstone with Tiny Planet, Charm Tears and Quad Shot.
Trivia
The term "brimstone" (burn stone) comes from the King James Bible's mention of burning sulfur. It is used in the phrase "fire and brimstone" to describe the torments of hell. While solid sulfur is yellow, molten sulfur is blood red.
Brimstone's item icon originally comes from the alchemical symbol for black sulfur, referred to as the Leviathan Cross. It was later adopted by Anton LaVey in The Satanic Bible to represent hell and is now often associated with Satanism.
Ironically enough, prior to update V1.7.5, Brimstone was changed such that it didn't contribute to the Leviathan transformation.
Brimstone has the same appearance of The Pact, but with big, curved horns and slightly less angry eyes.
Most items that change tear color will also give Brimstone an exotic appearance, but they do not combine and only one color effect is shown.
Brimstone is one of the few items that will give Isaac a unique costume when two copies are acquired, along with Guppy's Eye and Glass Eye.
The ram horns gained from picking up Brimstone were added as a cosmetic item to Team Fortress 2 to promote The Binding of Isaac: Rebirth. If the game was purchased before the 10th of December, players were awarded the item in genuine quality.
Bugs
Bug!
Picking up Brimstone before picking up Scorpio will not change the beam's color. Picking up Scorpio before Brimstone, however, will properly change it to green.
Bug!
When having Brimstone + My Reflection and facing towards an east/west wall, standing directly in front of it will make Isaac shoot in reverse — the front-facing oval Brimstone beam will shoot from the back, and the back-facing beam will shoot from the front.
Bug!
PC Brimstone will occasionally fire the laser the opposite direction.
Brimstone ticks 13 times over the course of 0.9 seconds (54 frames).
Brimstone ticks 9 times over the course of ~0.63 seconds (38 frames).
This item belongs to the 
Leviathan set. Collecting three items from this set will transform Isaac into Leviathan.
Azazel starts the game with a short-ranged, slower-charging version of Brimstone. Without the long-range version, his mini-brimstone won't have enough length to use any homing items.
20/20 will increase the number of beams accordingly, with exceptions listed below.
Tainted Azazel has a full-range, but thinner beam whose damage is halved unless enemies are cursed by his inherent 
Hemoptysis sneeze.
Bag of Crafting with eight 
Black Hearts.
The Inner Eye / 
Mutant Spider: Fires a spread of 2/3/4 Brimstone beams.
Almond Milk: Fires automatically upon reaching full charge. The beam lasts indefinitely as long as the fire key is held. The beam can change its direction while being fired, and can be aimed in any direction with joystick controls. The beam will also gain random worm trinket effects.
Apple! / 
Euthanasia / 
Tough Love: The beam can gain the damage multiplier from each of the items, although there is no visual difference. The bonus applies for the whole beam and not on a per-tick basis. Euthanasia loses its instant kill ability, however.
Anti-Gravity: An orb of energy expands, then shrinks while firing the beam after a delay. The orb still hurts enemies if they touch it. Isaac can start charging a new shot immediately after releasing the fire key without canceling the first shot, effectively allowing for a faster firing rate. It makes it harder to hit enemies with 
Soy Milk / 
Anti-Gravity + 
Incubus: Isaac will fire Brimstone orbs, while Incubus will fire regular Brimstone beams.
Brain Worm: The beam will curve 90 degrees in order to attack opponents, effectively acting as a stronger form of homing. Very strong against multi-segment bosses such as Pin or Mother.
Diplopia / 
Crooked Penny, adds another beam, with no increase in charge time.
Birthright effect, the laser beam will be 4× wider.
Chocolate Milk: Brimstone laser takes longer to fully charge, but can be released at any point. Width and damage of the laser increases with charge, from 25% damage and 50% width at minimum charge to 250% damage and 160% width at maximum charge.
Continuum: Brimstone laser travels through the wall and appears out the other side once.
Cricket's Body: Spawns split tears on the first enemy or obstacle the beam hits.
C Section: Shoots 4 fetus tears along with the Brimstone beam.
The Ludovico Technique: Fetus tears no longer fire with the Brimstone circle, even on doing damage.
Dead Eye: The damage multiplier that was gained before picking up Brimstone will now be permanent. However, saving and quitting the run will result in this damage multiplier being permanently lost (which is a bug).
Dataminer: Dataminer can be used to underflow Isaac's tears to immediately bring it to 120, maxing out Brimstone's width and damage via tears.
Epic Fetus: Adds a Brimstone Sad Bombs effect: missile explosions shoot ten beams in all directions, massively increasing damage and area of effect.
Explosivo / 
Sinus Infection: The beam has a chance to stick tears to enemies on every other tick.
Eye of the Occult: Creates a controllable crosshair similar to 
Marked. Fires automatically upon reaching full charge. The beam curves towards the crosshair and then attempts to hit the wall Isaac is facing.
Tech.5 / 
Technology 2: Tech.5 and Technology 2 lasers are also affected by the crosshair but cannot create the crosshair on their own.
Guppy: Blue Flies are spawned at a rate of approximately one blue fly per tick (
Haemolacria: +20 Tear Delay after Haemolacria's tears down. Tears burst into 4-7 Brimstone beams that do Isaac's damage per tick.
Technology: The lasers coil the beams. This is purely visual and does not grant a 1.5× damage multiplier.
Head of the Keeper: Makes the laser yellow and each tick has a chance to drop a coin.
Holy Light: Every tick of the beam has a chance of summoning a beam of light.
Hook Worm: Beam shifts left to right while firing straight and forms angles that constantly flatten and expand, effectively increasing its width.
Jacob's Ladder: Upon hitting an enemy, wall, or obstacle, the beam generates sparks that home in on enemies.
Lead Pencil: Lead Pencil triggers approximately every 2 seconds as the beam is fired (charge time is not counted).
Loki's Horns: Adds a chance to shoot a beam from all four cardinal directions, similarly to 
Head of Krampus's effect.
Lost Contact: Beam destroys projectiles, although only during its damage tick interval. The projectiles are not instantly destroyed when they touch the beam.
A Lump of Coal: The ring increases in diameter when Isaac is further; 100% when he is on the center, 1.25× when he is 12.5 tiles of distance away.
Mom's Knife: Overrides Brimstone.
Proptosis: The ring deals 1.5× Isaac's Damage at its largest, and 50% at its smallest. The ring increases in diameter when Isaac is closer; 1.25× when he is on the center, 100% when he is 12.5 tiles of distance away.
Mom's Eye: Adds a chance to shoot a beam from the back of Isaac's head.
Mom's Wig: Holding down a fire button to charge the attack very rapidly rolls the probability to spawn blue spiders; releasing to fire the beam, however, does not.
Monstro's Lung: Brimstone has priority. Does not apply Monstro's Lung's tears down. Fires 3-5 additional beams in random directions around Isaac. This effect also applies to 
Multidimensional Baby: If a brimstone laser is shot through the baby, it will double the laser.
My Reflection: Makes the beam curve when moving. It has the same effect on 
Mucormycosis: The beam has 25% chance to spawn spore to enemies on every other tick.
Mysterious Liquid: Leaves a creep for each enemy and obstacle the beam hits, on every other tick. 
Ocular Rift: Rifts may appear where the beam hits rocks, walls, or enemies.
Ouroboros Worm: The beam will make large loops on itself. The homing is present, but unreliable.
The Parasite: Spawns two perpendicular beams on the first enemy or obstacle the beam hits.
Rotten Tomato: Each tick of the beam's damage can mark enemies.
Rubber Cement: Beams bounce off of walls once, creating a second beam that deals 
If 
Sad Bombs: Upon exploding, bombs release ten beams in all directions.
Strange Attractor: Enemies are attracted towards the beam, improving its consistency. Consumables will also be moved by the beam.
Sulfur: Grants a larger beam with a 1.2× damage multiplier and +1 damage (same effect as picking up a second Brimstone).
Sulfuric Acid / 
Terra: The beam has a chance to destroy rocks every tick. The laser will not destroy sealed doors or open secret rooms.
Tammy's Head: Shoots ten beams in all directions. Given the item's single room charge, this makes for an extremely powerful synergy.
Cricket's Head or 
Magic Mushroom).
Tech X: Tech X has priority. Does not apply Brimstone's tears down. Fires a Brimstone ring. This Brimstone ring is larger than the laser ring and has a much wider hitbox.
Tiny Planet: The beam will wrap around Isaac once and then shoot straight forward.
Uranus: The beam will freeze any enemies killed by it, so long as they are not immune to the freeze effect.
Wiggle Worm: Beam becomes wavy while firing straight, effectively increasing its width.
Cursed Eye
Evil Eye
Eye of Belial
Flat Stone
Kidney Stone
Lachryphagy
Neptunus
Parasitoid
Pop!
Pupula Duplex
Technology Zero
Trisagion
8 Inch Nails: Beams gain knockback, pushing enemies away in the direction they travel but not out of their path. This increases its consistency.
Abyss: When Isaac uses Abyss to absorb Brimstone, it turns into a larger gray locust, but otherwise acts like normal locusts created by Abyss.
Bird's Eye: Will occasionally spawn a fire when firing.
Dr. Fetus: Overrides Brimstone.
Epiphora: Effect only activates when holding charge in a specific direction, and deactivates when the charge is released, effectively making Epiphora useless unless Isaac has exceedingly high tear delay.
Fire Mind: The beam will not cause explosions, but will still set enemies on fire.
The Forgotten: The charged attack will spawn a Brimstone ball that will float in front of The Forgotten for a few seconds before disappearing. The Forgotten will still melee attack while performing this action.
Ghost Pepper: The flames can still shoot from Isaac while holding the fire button.
Godhead: Homing and stat bonuses apply, but the beam does not have a damaging aura.
Ipecac: Does not apply Ipecac's stat changes. The beam poisons enemies.
The Ladder, when placed, will trigger the Ipecac-Brimstone explosions. (possibly a bug)
Isaac's Tears: Fires normal tears, but nearly instantly charges when charging Brimstone.
Knockout Drops: Gives the lasers high knockback.
Large Zit: Creep shots will still be fired occasionally while holding the fire button.
Lodestone: Changes the beam to gray, can still apply the magnetized effect. The beams are not attracted to enemies with the magnetized effect.
Number One: Although Number One is otherwise purely beneficial with standard Brimstone, 
Playdough Cookie: Brimstone will start cycling through colors and applies the standard chance of tear-effect on hit, with the homing effect occurring intermittently.
Spirit Sword: Overrides Brimstone.
Tainted Samson: Greatly decreases attack speed for Samson's rage mode melee attack and replaces the thrown jawbone with a large laser sphere (similarly to 
_appearance.png)
The Pact, but with big, curved horns and slightly less angry eyes.
Guppy's Eye and 
Glass Eye.
Bug!
Scorpio will not change the beam's color. Picking up Scorpio before Brimstone, however, will properly change it to green.
The Binding of Isaac: Rebirth
