Frederick Loren has invited five strangers to a party of a lifetime. He is offering each of them $10,000 if they can stay the night in a house. But the house is no ordinary house. This house has a reputation for murder. Frederick offers them each a gun for protection. They all arrived in a hearse and will either leave in it $10,000 richer or leave in it dead!

The story follows a family of inbreeds who have been afflicted by a genetic disorder known as ‘Merrye syndrome’, named after the family in which the disorder developed. This malady causes its victims to enter a state of age regression that starts at the age of ten and continues throughout the remainder of the person’s life, rendering them with the intelligence of a child. The final generation of the family has been entrusted to the care of the family chauffeur (Lon Chaney Jr), and all is well for these odd people until a greedy branch of the family decides that they want to relieve the family of its home. Mental illness has always, and will always be, a fascinating subject for horror movies as it probes into the unknown and Spider Baby makes best use of that fact.