Several weeks after the events of the first film, Brigitte Fitzgerald Emily Perkins uses monkshood extract to fight the effects of lycanthropy that transformed her sister Ginger into a werewolf. Brigitte shaves off excess hair, cuts her arm with a scalpel, and documents her injections and increasingly rapid healing rate, keeping a careful log of each change.
Ginger Fitzgerald [Katharine Isabelle] appears as an apparition and warns that monkshood only slows the transformation progression and is not a cure. Regardless, Brigitte has become addicted to monkshood. Brigitte senses the presence of a male werewolf that has been relentlessly stalking her with the intention to mate, so she quickly packs and opens the door. She is found by Jeremy [Brendan Fletcher], a flirtatious librarian who has brought to her several books she attempted to check out earlier. He sees that Brigitte has toxic shock syndrome, and Jeremy attempts to bring her to a hospital; however, the male werewolf mauls him to death. Brigitte escapes but is too sick to go on. She stumbles down the street and collapses in the snow.
Brigitte wakes in an in-patient drug rehabilitation hospital, from which she unsuccessfully attempts to escape. She pleads to be released, but Alice [Janet Kidder], the clinic's director, refuses; however, Brigitte palms a piece of glass to continue to measure her healing. Tyler [Eric Johnson], an orderly at the clinic, offers to trade monkshood for sexual favors, which she declines. As her healing rate continues to accelerate, so does her rate of transformation and the dose of monkshood needed to resist it. Ginger continues to appear, taunting Brigitte as she experiences growing cravings for sex and murder, which Ginger also had. During a group therapy session, Brigitte fantasizes about her stretching class being instructed to lie on the floor and violently masturbate; a vision of Ginger jolts her back to reality, and her palm is revealed to be covered in hair. Later, a despondent Brigitte holds the shard of glass to her throat, but she does not go through with it.
While at the clinic, a girl named Ghost [Tatiana Maslany]—the granddaughter of Barbara [Susan Adam], a severe burn victim at the hospital—follows the clinical staff, who discuss Brigitte's injections of monkshood, and realizes Brigitte's secret. Ghost slips Brigitte a werewolf comic book and begins to question her about lycanthropy. When Ghost notices that Brigitte's ears have become pointed, Brigitte cuts off the tips. Ghost, now convinced of Brigitte's lycanthropy, attempts to slip Brigitte monkshood, but Tyler prevents it. In despair at her rate of transformation, Brigitte allows Tyler to inject her. After the male werewolf tracks Brigitte to the clinic, she and Ghost plan their escape. They crawl through air vents to reach the basement, where they encounter Beth-Ann [Pascale Hutton], an addict who traded sex for drugs. The male werewolf kills and drags away Beth-Ann, and Brigitte is wounded after she fights the werewolf, but her wounds heal almost instantly.
Ghost drives them to Barbara's house and explains that Barbara fell asleep with her bedtime cigarette. The next morning, Brigitte eats a dying deer while it is still alive. Brigitte realizes that her rate of transformation is progressing too fast, and with no other choice, the duo arrange a meeting at a gas station with Tyler to procure more monkshood. When Brigitte wanders in the gas station, she discovers the attendant has been slain. Brigitte quickly returns to the car to find Tyler arriving, and, when they return to Barbara's house, Tyler administers monkshood to Brigitte, which her body violently rejects. Worried, Tyler calls Alice.
Jealous of the attention that Tyler is getting, Ghost tricks Brigitte into thinking that Tyler abused her, causing Brigitte to lock Tyler outside, where the werewolf kills him. Alice arrives, and Ghost attacks her with Barbara's hunting rifle. Alice confronts Ghost about her delusions, and Brigitte, discovering that Barbara is not a smoker, aggressively pins Ghost against the wall and argues with her; she realizes that Tyler did not abuse Ghost, and Ghost burnt Barbara. Alice attempts to take Ghost with her but retreats to the attic once the werewolf breaks in through a window.
Brigitte, whose transformation is almost complete, lures the The Beast Jake McKinnon into a room. Brigitte stabs him while Ghost distracts the werewolf. The werewolf bites Brigitte, and, as they struggle, they both fall into the basement, where the werewolf is impaled on a booby-trapped mattress. Ghost kills Alice with a hammer, and a weakened Brigitte begs Ghost to kill her before the transformation completes. Instead, Ghost locks her in the basement and illustrates a comic book that depicts herself as a powerful warrior with a werewolf pet. Ghost narrates that Brigitte is getting stronger and is waiting to be unleashed on her enemies. A doorbell is heard, and Ghost prepares to welcome Barbara home.
