In the Louisiana Bayou town of Marsh Island, two farmers, Royal Dano and John Davis Chandler, stumble upon the mauled, dead body of a local young woman. Sheriff Aaron Whitaker, David Janssen, is summoned to the scene. The victim's temperamental brother, Geoffrey Lewis as Lawrence Burrifors, leaps to the conclusion that the girl's lover — a man whose name the brother does not know — must be the killer. The town's doctor, John Beradino as Dr. Druten, examines the body and rules that the victim died from a blow to the head.
The sheriff's investigation unleashes a chorus of theories from wary townsfolk: some insist wild dogs are to blame, while Burrifors remains convinced of a mysterious lover. A posse forms to chase the wild dogs, but the search proves fruitless. Burrifors keeps pressing his lover theory, even as the sheriff grows suspicious of him. The dying father, Hugh Burrifor, warns the sheriff about the loup-garou, a term the lawman doesn’t understand, adding an eerie layer of folklore to the case.
As clues point toward the plantation home of the wealthy Rodanthe family, the sheriff suspects that Andrew Rodanthe, Bradford Dillman, may have known the victim and even had an affair with her. The Rodanthe siblings—Andrew and his sister Louise, Barbara Rush—represent the last of a storied local dynasty. Andrew claims he was struck by an attack of malaria on the night of the murder, a detail the sheriff weighs as he follows a trail of tension and suspicion. Tensions intensify when Lawrence assaults Druten, and the doctor’s life is imperiled; the situation culminates in a brutal act of violence as, during a full moon, Lawrence and the sheriff’s deputy are killed when the cell’s bars are ripped from the wall.
With danger escalating and the town growing fearful, Andrew volunteers to become a deputy. The sheriff and Andrew return to Hugh Burrifor’s house, where they uncover a voodoo potion that emits a vapor intended to repel the Rougarou. Andrew inhales the potion and experiences what appears to be an epileptic seizure, sending him to the hospital for observation. At the hospital, Louise reveals her fluency in French and offers to consult Hugh Burrifor about the mysterious term Rougarou. Conversing with the old man, Louise deciphers the word as Rougarou, a mispronunciation of Loup Garou, which in English translates to werewolf.
Transformed into a werewolf, Andrew breaks free and becomes the focal point of a desperate manhunt. As the town bands together, Louise urges the mayor to consider remedies, sharing a family secret about her grandfather’s past spells of illness that hint at a hereditary werewolf curse inherited by Andrew. Louise returns to her plantation home, and the werewolf Andrew enters the house in pursuit. She flees to the barn, trying to set the creature alight, but the beast outsmarts the blaze and presses the chase back into the house. In a final confrontation, Louise shoots Andrew just as the sheriff arrives; the victim dies, and Andrew reverts to his human form.
