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A small island off the coast of Greece holds a secret so dreadful, that once you step on its shore, you must remain there forever. General Nikolas Pherides (Karloff) is such a visitor. He came to honor the grave of his wife, and discovers that the entire island has been overrun with a plague - a sickness that drives the victims insane. Soon, Pherides succumbs to the illness. When insanity runs rampant, grave robbery, premature burial and vampires are the unspeakable horrors that await those on the Isle of the Dead.