The movie starts with Peter narrating what he says will be a very strange story that he experienced. Bruno (Lon Chaney Jr) is the caretaker for three demented siblings, Elizabeth, Virginia and Ralph Merrye (Sid Haig). Virginia is obsessed with spiders, and likes to catch and eat insects. She also has a large rope web, in which she tries to catch and eat humans. The three suffer from "Merrye Syndrome", a genetic affliction unique to this family. It causes a mental degeneration, where they come to act like simple savage beasts. Bruno is a servant, who promised their father that he would remain and care for them.
Peter and Emily are relatives. They show up unexpectedly with a lawyer. They want to declare the siblings incompetent, and take over the home and fortune. Ralph rapes Emily. The siblings kill the lawyer. Three elderly aunts escape from the basement, they kill and eat Emily. Bruno realizes it is impossible to control the siblings or keep the police out at this point. Bruno buys dynamite. Bruno frees Peter. Peter escapes just before the house explodes. Bruno, the three siblings and the aunts from the basement all die.
The movie ends again with Peter narrating. He relates that he inherited a fortune, and the disease died out with the last of the Merrye family. He claims that as a distant relative, his family is not affected. We then see his daughter playing with spiders, and acting a lot like Virginia.
Thanks Joseph C!