A pathologist experiments with a deaf-mute woman who is unable to scream to prove that humans die of fright due to an organism he names The Tingler that lives within each person on the spinal cord and is suppressed only when people scream when scared.

In 1880, Sir Robert Cargrave, a London physician known for his experimental work in paralysis treatment, is summoned to Gorslava by the mysterious Baron Sardonicus—who is now married to Cargrave's former wife, Maude—to treat his disfigurement. When Cargrave arrives, he finds the masked baron is a cruel sadist who has threatened to harm Maude if he is not successfully cured.