In the jungle of the Venezuelan Amazonas, the specialist in spiders, Doctor James Atherton, is researching an unknown species of spider recently discovered. His photographer Jerry Manley is bitten by one spider and his body is sent to his hometown Canaima with one spider hidden in the coffin. She escapes and hides in a barn of a house. Dr. Ross Jennings moves with his family from San Francisco to the small town Canaima seeking for a peaceful place to raise his son and his daughter. He has had a trauma with spiders since he was two years old. However, the spider built a nest in his barn and his basement and has reproduced. The town is infested of the mortal species of spider from Venezuela, and Dr. Ross, together with Doctor James Atherton, his assistant Chris Collins and the exterminator Delbert McClintock try to find the nest to destroy the queen and end the menace.