In a long-running Los Angeles nightmare, four years of brutal murders have left the city unsettled: men are found dead with huge puncture wounds in their chests, the victims' bodily fluids drained, and the wounds filled with some kind of venom. The pattern draws private detective Mark Higbie into the case after a tense bar encounter where a mysterious, dark-haired woman with a German accent tries to help a broken-down car and a friend nearby ends up dead minutes later.
As Mark delves deeper, he discovers that Lieutenant Gully Conti is aware of the culprit but is muting details to protect a larger motive. The investigation uncovers a chilling thread: every killing leaves behind signs of a spider’s venom, and informants point to a woman named Valerie Steffan who seems to appear around the crime scenes. Suspicion initially falls on the Lockwood sisters, Leigh Lockwood and Laura Lockwood, whose lives echo the androgynous pattern of danger surrounding the victims. Leigh, worried about the police narrowing the search to her family, hires Mark to help uncover the truth while downplaying the police focus on her.
Mark learns of a witness—a former bartender—who swears one killer was a man-sized spider, a detail that shifts the case from fantasy to a terrifying possibility. He digs into the Lockwoods’ past and discovers a plane crash that claimed their father and left a daughter nearly fatally attacked by spiders years earlier on the family vineyard. An aging Native American elder recounts an old legend: some women, under stress during a full moon, transform into giant, nearly indestructible spiders guided by a curse carried in their female line. Those affected bear a red hourglass-shaped birthmark on their abdomens, just like the spiders, and fire is the only force that can kill them in spider form. The elder’s tale hints that the twins’ bloodline may carry this curse, and the twin who was bitten is the one truly cursed.
Mark’s investigation brings Laura into focus, and a devastating truth emerges. Laura’s sister Leigh learns that Laura’s fragility runs deeper than simple jealousy. Laura has long suffered from multiple personalities, with Valerie as the dominant, embittered facet that uses the curse’s power. Valerie has pursued Leigh’s partners, and when rebuffed, she becomes a spider to murder them. The family’s secrets are tightly kept: their mother, and their former nanny, Olga, are the only other people who know the terrible truth. Their mother has fallen into a catatonic state after witnessing a killing, a trauma that haunts the household.
As Leigh races to escape, Valerie visits and taunts their mother while revealing how Laura’s past—especially a painful relationship with Gianni, who assaulted Laura and fathered a child—fed the killer’s rage. In a brutal culmination, Laura turns into a spider, and the family’s mother tragically dies; Olga arrives too late to prevent the tragedy. Mark follows a lead to an old farmhouse where Leigh, terrified, waits as Valerie breaks through Laura’s defenses and claims the scene. When Mark confronts the spider, his pistol fails to stop Valerie, but a thrown lantern catches her, and fire consumes the creature. The farmhouse burns, and the immediate danger appears to be resolved.
In the quieter aftermath, Mark returns to Leigh’s seaside home for dinner, where their daughter Jennifer is introduced—an ordinary child by appearance, but with a chilling sign. Jennifer is shown playing on the beach with a dog, and Leigh explains that Jennifer is adjusting to life with her, though she bears occasional nightmares that lessen over time. The final, unsettling reveal lands on Leigh as she notices Jennifer, who does not resemble her, wave from the balcony. A red hourglass-shaped birthmark on Jennifer’s abdomen confirms the horrific truth: Laura is Jennifer’s mother, and the “curse of the black widow” has been passed down, hinting that the spider myth may live on in the next generation.
