Inspector Lohmann's eagerly awaited fishing holiday is put on hold when he is called to investigate the murder of a man found in a railway tunnel. He was an Interpol courier carrying proof of the Chicago Syndicate's planned cooperation with a European criminal organisation that was in an attache case chained to, but now missing from his body. The Inspector gets word from Washington D.C. that a female representative of the Syndicate, Mrs. Pizarro is currently in Europe to meet up with the European criminals, and that the Federal Bureau of Investigation is sending Special Agent Joe Como to liaise with the German authorities. Lohmann visits a prison to have a meeting with one of the prisoners, Alberto Sandro, who was a member of the European criminal organisation in an unsuccessful bid to learn more about the upcoming events.
Mrs. Pizarro is murdered by a flame thrower with Inspector Lohmann dodging questions from female reporter Maria Sabrehm who happens to be near the location of the murder, as is Joe Como. The only witness is a blind man who recalls the distinctive sound of a man with a wooden leg before he felt the heat of the flamethrower. Lohmann discovers a book on the charred body of Mrs. Pizarro called The Devil's Anatomy written by Reverend Briefenstein of St. Thomas Church. Lohmann looks through the book whose thesis is that though the Devil is a spirit, he can manifest himself into doing evil by taking the form of a werewolf, vampire or Dr. Mabuse. Lohmann, followed by Como and Maria meets the Pastor in his church to ask about Dr. Mabuse who everyone believes is dead. The Pastor says that though a man's body can die, his soul can infest the bodies of other men. The voice of Dr. Mabuse comes over the speaker system of the church warning Lohmann to stop his investigation. As Lohmann wanders through the church, Joe Como engages in a conversation with Mabuse saying he is really Nick Scappio, the representative of the Chicago Syndicate who is there to negotiate a shipment of a new drug into the United States. However, before the Chicago Syndicate will cooperate they demand to see proof of the power of the drug.
Following his only lead, Lohmann goes to obtain further information from the blind witness who is run over and killed. Como and Lohmann pursue the murderer that turns out to be Alberto Sandro who has apparently escaped from the prison. Recapturing him, the prison authorities, who maintain an industrial laundry allowing trusted prisoners to deliver and pick up cleaning in the community, deny Sandro has left the prison. The warden insists Sandro is sedated in his cell. They discover that the person in Sandro's cell is a dead man with a wooden leg who the blind man had identified.
Dr. Mabuse's drug, invented by Maria's scientist father who is a prisoner in the same prison as Sandro, is a mind control device capable of turning a person into a zombie whose actions can be controlled by radio transmissions. Mabuse not only has an army of criminals who can come and go from the prison but can be commanded to do criminal acts that they will have no recollection of later on. In the meantime Lohmann's assistant gets the fingerprints of Como and transmits them to FBI headquarters who declare that the fingerprints of the man calling himself Como is not the real Agent Como. Como/Scappio is sent to the prison. He discovers Dr. Mabuse's display of the power of his drug to the Chicago Syndicate will come on Friday the 13th (the date of the film's premiere); when every prisoner will be injected with the mind control drug, armed with weapons and released in order to launch an armed assault to destroy a nearby nuclear power plant.