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Six months after the events of Underworld: Evolution, humans have captured Selene during "The Purge", a global military crusade to exterminate vampires and lycans. Vampires have waged guerrilla warfare against the government, but the humans have overrun them, forcing survivors to hide underground and resist the humans on their own.
Twelve years later, human governments have concluded their campaigns against the vampires and lycans. They have annihilated 95% of the vampire race and believe lycans to be extinct. Selene, dubbed "Subject 1", is freed from cryogenic suspension by "Subject 2" and escapes the medical corporation Antigen. The corporation is