After being forced to leave Bohemia due to his mad experiments, Baron Victor Frankenstein lodges at a boarding house in Austria-Hungary run by Anna Spengler and builds a secret laboratory in his room.
Anna's fiance Karl Holst is a doctor at the local insane asylum where Frankenstein's former assistant, Dr. Frederick Brandt, now resides after suffering a mental breakdown due to Frankenstein's experiments.
Frankenstein discovers Karl has been stealing narcotics in order to support Anna's ailing mother. In exchange for not reporting Karl to the authorities, Frankenstein blackmails him into assisting him with the kidnapping of Brandt in order to cure his sanity so the two can continue their work together. Karl reluctantly agrees to help him.
While Karl is attending to Brandt, Frankenstein rapes Anna and blackmails her into not telling Karl.
Meanwhile, Brandt has a heart attack, necessitating Frankenstein and Karl to kidnap the asylum's administrator, Professor Richter, so they can transplant Brandt's brain into his body and save him. They succeed and bury Brandt's body. The body is soon exhumed by the police, forcing Frankenstein, Karl and Anna to relocate to an empty house with Brandt.
Later, Brandt recovers and Anna lets him escape. Enraged, Frankenstein kills Anna and goes after Brandt.
Brandt makes it to his former home, but his wife Ella refuses to believe he is her husband. Wanting revenge and knowing Frankenstein will eventually find him there, Brandt allows Ella to go free and waits for Frankenstein.
Frankenstein soon arrives, and Brandt sets the house ablaze to trap him. Karl arrives to avenge Anna’s murder, but Brandt shoots him, presumably killing him. The film ends with Frankenstein and Brandt apparently dying in the fire.
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