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|“||So he carried me away in the spirit into the wilderness: and I saw a woman sit upon a scarlet colored beast, full of blasphemy, having seven heads and ten horns.||”|
A crescent moon and 5-point star, both black with a red outline.
When Isaac falls to his last half of his last red heart without soul or black hearts, a message reading "What a horrible night to have a curse." appears on the screen and the player becomes the Whore of Babylon.
This increases Isaac's Damage by 2.16 and Speed by 0.36; he will stay in that form until leaving a room with more than a half-heart (soul hearts do not count.) When the player enters a room with the item's effect already activated, the damage increase is 1.5 and the speed increase is 0.3. When activated via III The Empress, increases damage by 3.375 and speed by 0.45 until end of room.
If ??? picks this up, he permanently gains its effects upon leaving the room for the remainder of the game.
- When the Whore of Babylon is activated, it will give Isaac 3 seconds of invincibility, as opposed to the usual 1 second of invincibility from taking damage (2 seconds from full heart damage). This can be used to get free Coins from Blood Donation Machines when Whore of Babylon activates.
- If Isaac takes a full heart damage with only one heart remaining, he will die and Whore of Babylon will not activate.
- Eve's Whore of Babylon will activate when she falls to her last red heart.
- Any items that give Isaac Flight (with the exception of Spirit Of The Night) will also give him black wings, if the player has the Whore of Babylon. This also applies to any Devil Room item that turns Isaac black/demonic, such as The Pact or Brimstone.
- The Dead Bird does not spawn upon Whore of Babylon's activation, assuming no damage was taken before in the room.
- Guppy's Paw - Helps the player to reduce the amount of normal health to increase the chance to trigger the transformation.
- IV Bag, Razor Blade, Blood Rights or Kamikaze - These items require a health payment in order to be used, thus helping the player trigger Whore Of Babylon more often while also preserving soul hearts.
- The message that is displayed when the item takes effect is a reference to Castlevania 2: Simon's Quest.
- The item's appearance is similar to the Curse Room symbol, as shown on the minimap.
- The biblical Whore of Babylon is mentioned in the book of revelations 17:4-18. While the meaning is debated, the Whore is one of the figures relating to the end of the world associated with the Antichrist and Beast of Revelation. She is the epitome of the concept of sexuality as a form of evil, following from Eve as the root of that sin, which is why Eve starts with the potential to become the Whore.
- The item's symbol also resembles the backwards symbol of Islam.