A man in Milwaukee is running through a crowded parking garage during rush hour. A huge man-shaped creature is pursuing him, catches him, and rips him apart.
The next day, veterinarian Wilbur Orwell is at home eating a jelly doughnut and spilling most of it on himself. He listens as the news reports about the apparent animal attack, and barely listens to his son Oliver when he points out that his father has jelly on his shirt. As Wilbur tries to clean off the jelly, his wife Patty comes in and tells him to change his shirt and then takes Oliver to school.
Wilbur goes to his office and goes through a number of typical animal cases. At lunch, his secretary Mikayla complains that the other doctor, Geoff Matthews, still hasn't come in. She tells Wilbur that he lets Geoff take advantage of him but Wilbur isn't concerned. Once she leaves, Wilbur makes a half-hearted attempt to call Geoff but gets no answer. He's interrupted when he hears yells from the lobby. Wilbur goes to investigate and a trucker is there, explaining that he hit a strange animal that jumped in front of him on the road. Wilbur and Mikayla get the huge animal into the exam room, and Wilbur finds a set of dog tags on it bearing the name "Michael." The creatures go berserk, knocking Mikayla to the floor and biting Wilbur on his arm. It dies from its injuries and Wilbur faints in shock. He soon wakes up, treats his wound, and gives himself an injection for rabies.
That night, Wilbur is trying to sleep but moaning in pain. Patty comes in and turns on the light, and Wilbur complains about the brightness. When his wife tries to flirt with him, Wilbur says that he's too tired. Disappointed, Patty wonders if he's even attracted to her anymore. She finally notices his arm wound, bleeding through the bandage, and asks if he's all right. Wilbur tells her to open the window for some fresh air and passes out.
The next morning, Wilbur wakes up and hears a radio report about several more animal attacks. Wilbur instinctively sniffs at Patty, asleep next to him, and goes down to breakfast. He tries to eat a jelly doughnut bit with his now-heightened sense of smell, he can't stand it. On the television, Detective Marvin Deane is giving a press conference but has nothing specific on the animal attacks. Wilbur turns off the TV, much to Oliver's surprise when he comes in, and is paying enough attention to cheerfully greet him.
Wilbur goes to the clinic and examines the animal's corpse, and is surprised to discover that it has fillings and pierced ears. A couple, Crane and Moonflower Dougdale, arrive to claim the body and are clearly upset. Wilbur is surprised that they're so concerned about a mere pet, and the Dougdales ask for the body so that they can give it a proper burial. It's against proper procedure for animal disposal but Wilbur finally gives in. As they put the body in their car, Wilbur gives them the dog tags and asks what kind of animal it was. Crane avoids the question but gives Wilbur their card for their pottery business.
That afternoon, Mikayla complains to Wilbur that Geoff is late again. Wilbur takes command and tells her that she's right, much to her surprise. Geoff finally answers the phone while playing video games, lies, and tells Wilbur that something came up. He then fakes static on the line, says that he'll be in tomorrow, and hangs up on his boss.
When Wilbur comes home that night, he discovers that Patty has gone out for the evening. He dozes off on the coach and wakes up when Patty comes home. She tells him that he forgot Oliver's spelling bee and that their son is up in his room, upset. Wilbur tries to apologize, saying he had a busy day, but Patty warns him that she and Oliver have both had enough of his excuses. The veterinarian goes upstairs and tries to apologize to his son, but Oliver tells him to go away. Depressed, Wilbur goes out on the patio and checks his wound, and is surprised to discover that there's no sign of the bite. As the moon comes up, Wilbur starts to moan in pain and transform.
Geoff is walking through an underpass while receiving a text message from his girlfriend, Kathy. As he starts to respond, something attacks him and rips open his face.
The next morning, a happy Wilbur wakes up and hears a news story on the radio about Geoff. As he gets up, Wilbur discovers that his feet are covered in mud and a trail leads to the open window. On the television news, Deane is telling the press that an animal is still responsible and there's no indication that a serial killer is at large. A smiling Patty tells Wilbur that he was incredible in bed the previous night and calls him an animal. When Wilbur appears confused, Patty wonders if he even remembered what happened, and Wilbur hastily lies and reassures her that it was fantastic. Oliver comes down, still mad at his father and ignoring his overtures to make up. As he prepares to go to work, Wilbur puts on a pair of dark glasses and growls playfully at his wife.
At the clinic, Wilbur is examining a photo of the Michael creature when he smells Mikayla behind him. She says that Geoff hasn't come in yet again, but Wilbur tells her that they won't be seeing Geoff anymore. The veterinarian offers her a full-time position as a veterinarian which she gladly accepts, and then goes to work. Wilbur finds new joy in his work and is able to diagnose animals just by touching and smelling them.
Deane comes to visit and asks Wilbur about the recent animal attacks. The detective wonders if a pet might have gone bad, but Wilbur suggest it must have been a larger wild animal. When he realizes that Deane is about to see the photo of Michael, Wilbur tries to distract Deane from noticing it. Deane finally tells him that Geoff was attacked and killed, showing him photos of the dismembered body. The detective hints that he thinks Wilbur is involved and notes that he seems to know a lot more than saying. When Deane accuses him of committing the murders, Wilbur remains silent and the detective leaves, warning him that he'll be in touch.
As Wilbur contemplates his reflection in the mirror, Mikayla comes in and asks about Michael's body. She wonders if it might have come back to life and Wilbur decides to talk to the Dougdales. He goes to their pottery shop and home and offers his condolences to Moonflower, and then shows her the bite on his arm. Wilbur's eyes glow yellow and Moonflower, smiling, reveals her glowing yellow eyes as well.
The Dougdales invite Wilbur to have coffee with them and he wonders how they've controlled the change. The old hippies explain that they consider the transformation a way of communing with nature, and Wilbur has to admit that the transformation has changed his life for the better. He worries that he may have committed the murders without remembering, but Crane tells him that from previous experience, he can assure Wilbur that a werewolf doesn't do anything that the human wouldn't do. He assures Wilbur that he isn't responsible, and that they're vegans and never kill anyone, but warns that there are other werewolves in the world that aren't as pleasant.
Mikayla is walking home from the office and waits at a bus stop. The creature attacks her, slashing at her face repeatedly.
When Wilbur hears about the attack, he goes to the hospital to see Mikayla. Deane is there and informs the veterinarian that a patrol car scared off the killer before he could finish killing Mikayla. The detective suspects Wilbur more than ever, figuring that he wanted to get rid of another employee. Wilbur goes to the unconscious Mikayla and smells the killer's scent on her hand. Ignoring Deane's warnings that they'll get an eyewitness account from Mikayla when she wakes up, Wilbur runs out to follow the scent.
The scent leads through the city to an old warehouse and a loft apartment. Wilbur goes inside, removing his clothing, and discovers that the walls are covered with graffiti worshipping werewolves. The scent leads to the apartment door and Wilbur, now fully transformed, smashes through the door. A man, Forest J. Caldwell, is sitting in a chair in front of his television. When he sees Wilbur, Caldwell says that he's beautiful and kneels down before him. He explains that he killed the people so that he would attract a werewolf's attention because he wanted one to come and bite him, making him the one thing he always wanted. Caldwell takes out the crude werewolf costume that he used to commit the murders and shows it to his visitor. Wilbur hesitates and Caldwell says that he'll find Mikayla and finish the job. The werewolf, furious, rips off Caldwell's arm and then tears him apart. Once his rage fades, Wilbur transforms back to normal and staggers off.
A few months later, the Orwells invites the Dougdales and a recuperating Mikayla to their home for a meat-free Thanksgiving. Oliver is happy with his new and improved father and Patty with her new husband. She goes out into the kitchen and Wilbur follows her out, smilingly telling the others that they may be a while. Once alone, Patty admits that everyone is in awe of Wilbur since he's become a new person. Wilbur says that he's in awe with her, kisses her, and says that he wants to share everything with her. She agrees and Wilbur playfully bites her.