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At Chad's Café in the rural town of Mountaincrest, Duncan March, a darkly troubled stranger, leaves the premises and is accosted in the alley by a man who demands his money. While Duncan fends off his attacker, a startled woman in the street hears the sounds of panting and growling emanating from the alley and screams. After March flees into the night, Clovy, the deputy sheriff, finds the body of the thief, whose throat has been ripped open. Joined by two citizens, Clovy follows the killer's footprints in the snow and is mystified when the shoeprints suddenly turn into animal tracks. Clovy sends his companions back to town to summon Sheriff Jack Haines while he waits by the tracks. When Jack arrives, he finds Clovy injured, his shoulder clawed, and takes him to see Dr. James "Doc" Gilchrist and Gilchrist's niece, Amy Standish, who serves as his nurse. As they listen in dismay, Clovy describes his assailant's hand as being covered with hair, leading Jack to conclude that their prey is a werewolf. In the snow-covered hills above Mountaincrest, meanwhile, March cowers barefoot in the cold, and noticing the paw prints surrounding him exclaims that it was all a terrible dream. As reporters, alerted by the local undertaker about the killing, flock to town to investigate, Jack sets up a series of roadblocks ringing the area. Attracted by Doc's shingle, March seeks help at his house and confides that he is suffering from amnesia and cannot remember a thing since being involved in an automobile accident and taken to see a doctor. When March confesses to killing a man the previous evening, Doc expresses disbelief, frightening March, who then runs out of the house. Speeding to Jack's office, Amy and Doc relate the story of March's visit and Amy pleads for clemency on his behalf. Meanwhile, at a laboratory in a nearby town, doctors Emery Forrest and Morgan Chambers, the physicians who treated March after his accident, read an account of the killing. Morgan, who believes that radioactive fallout from the hydrogen bomb will destroy mankind, has been trying to develop an inoculation against radiation, and tested his formula on March. Alarmed by March's transmutation, Morgan asserts that his former patient must die and sets out with Emery to kill him. Stopped at the roadblock outside of Mountaincrest, the doctors are allowed to pass after explaining that the killer was their patient. After they track March to a mine tunnel in which he has sought refuge, March begs for help, but then, sensing danger, transforms into the werewolf and lunges at Emery. Morgan fires his gun, driving March away, and the sound of the gunshots attracts Jack and his posse, who converge at the tunnel. Although Morgan explains that March was his patient, Jack remains suspicious of the doctor's motives. After the creature slaughters and devours a sheep, Jack decides to set up a series of bear traps to catch him. Soon after, March's car is found on the outskirts of town, and his unsuspecting wife Helen and young son Chris come to Mountaincrest in search of their loved one. Jack arranges for them to stay with Doc and Amy, but before they arrive, March stumbles into one of the traps, then pries it open and escapes, turning back into a man. At Doc's house, Helen wonders why everyone is being so evasive about her husband when she overhears Jack tell Amy that March was caught in a trap and insists on joining the search for her husband. Jack, Amy, Helen, Chris and Clovy then start combing the hills for March, calling to him through a loudspeaker. Spotting his father hiding behind some trees, Chris runs to him. After embracing his son, March begs them to go away and then collapses. Brought back to town and locked in a cell, March again pleads with his family to leave before he changes back into a beast. After assigning Clovy to guard the jailhouse, Jack goes to Doc's house, and Doc, hoping to develop a cure for March, decides to send a vial of his blood to the lab. Meanwhile, Morgan and Emery trick a drunk into accompanying them to the sheriff's office, and when Clovy goes outside to investigate, they drug him. When the doctors enter March's cell, he changes back into a werewolf and attacks. Drawn by the sounds of blood-curdling screams, Jack and the rest of the town run to the jailhouse, where they find Morgan and Emery mauled and March missing. In the dead of night, Jack organizes a manhunt for March, and the group flings torches at the fugitive to frighten him away. The next morning, they track him to a bridge above the highway, but when March refuses to surrender, they are forced to shoot him down. As he dies, March turns back into a man for the final time.