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In 1920s England, Dr. Anton Phibes, caped and shrouded in long black robes, vigorously plays his organ, then waltzes in his elaborate movie-palace-like mansion with his beautiful, mute assistant, Vulnavia, while an orchestra of mechanical puppets serenades them. Phibes, a mechanical genius as well as an accomplished organist, then loads a cage swathed in black cloth into his limousine and drives off with Vulnavia. In another part of town, as Dr. Dunwoody slumbers in his bed, Phibes lowers the cage through a skylight into the room and releases a flock of vampire bats. After Dunwoody's shredded body is discovered the following morning, Inspector Trout is called to investigate and recalls that another surgeon was stung to death by bees the previous week. Meanwhile, back in his sanctuary below the main floor of his house, Phibes, still cloaked, drapes an amulet over a wax bust of Dunwoody, which he then sets on fire. Afterward, Phibes cements a prosthetic nose and ears to his face and dons a wig. At a lavish costume party that night, Phibes hands one of the guests, Dr. Hargreaves, a frog mask and fastens it with a latch. As Hargreaves ascends the staircase, the latch begins to contract, strangling him to death in front of the startled guests. Although Trout perceives a pattern of torture in the deaths, his superior scoffs at his assumption. The following night, as Dr. Longstreet watches a lurid film of a snake dancer at his house, Vulnavia enters the room, sheathed in a floor-length, white fur coat, and seductively binds him to a chair. Phibes then appears, plunges a needle into Longstreet's arm and begins to draw out his blood vial by vial, until he is drained dry. As Longstreet suffers death spasms, he grabs Phibes, dislodging an amulet from Phibes's pocket. After Trout discovers that all the victims worked with Dr. Vesalius, he goes to visit the surgeon. Vesalius is at first skeptical about Trout's assumption that he is connected to the murders until a phone call for the inspector reveals that Longstreet's body has been discovered. When Trout takes the amulet found next to Longstreet's body to the jeweler who made it, the jeweler identifies it as one of a set of ten Hebraic symbols commissioned by a mute, attractive woman. Trout then takes the amulet to a rabbi, who recognizes it as the Hebraic symbol for blood, one of the ten plagues that beset the Pharaoh of Egypt for enslaving the Israelites. The rabbi lists the plagues in order: boils, bees, bats, frogs, blood, hail, rats, locusts, the death of the first born, with the final curse being that of darkness. Meanwhile, in his sanctuary, Phibes attaches a speaker to a hole in his neck and through a phonograph amplifier, speaks to a photo of his dead wife, vowing that all those who killed her will now die. Vesalius, realizing that Trout's theory may be correct, shifts through his case files, narrowing them down to only one instance in which all the victims worked together, the case of Victoria Regina Phibes, who died during an operation. Vesalius then tells Trout that when he cabled Victoria's husband in Switzerland, the man raced back to England, but in his haste, his car crashed and he burned to death, after which he was entombed next to his wife in the family crypt. When Trout investigates Phibes's trip to Switzerland, he learns that the doctor's bank account was transferred to England by a tall, attractive woman. Meanwhile, Vulnavia, smartly dressed, stops her car along the roadside where she attracts the attention of Dr. Hedgepath, who is being driven by his chauffeur. Hedgepath instructs his chauffer to help Vulnavia, and as the man leans over to examine the car's engine, Phibes knock him unconscious, then places a hose inside the limousine and locks Hedgepath in the back seat. After the chauffeur's unconscious body is found, Trout is summoned to the scene of the crime and finds Hedgepath frozen to death in the back seat of his car, his body encased in hail spewed from the hose. One night, as Vesalius and his son Lem, an avid piano player, are playing chess, Lem tells his father about a conversation he had with Darrow, the owner of the music shop, in which Darrow mentioned a man named Phibes as an example of a great organist. Vesalius then goes to question Darrow, who reveals that Phibes is his patron. When Vesalius relays the information to Trout, the two open the Phibes family crypt and discover that Victoria's sarcophagus is empty, leading Trout to believe that Phibes is still alive. Now certain that doctors Kitaj and Whitcombe, who also presided over Victoria's case, are in danger, Trout sends his assistant, Sgt. Schenley, to warn Dr. Kitaj. Kitaj is just taking off in his private plane when the sergeant arrives, and as the sergeant races his car down the airstrip, the doctor becomes airborne. Soon after, rats swarm into the cabin and attack Kitaj, who loses control of the craft and crashes. Concerned that Whitcombe may be the next victim, Trout meets the doctor at his club and is about to whisk him off to the safety of a country retreat when a brass bust of a unicorn catapults through a window, impaling Whitcombe on its horn. Worried about the safety of Nurse Allen, who assisted in Victoria's operation, Trout seals off the hospital in which she works and confines her to her room. As she slumbers, aided by a sleeping pill, Phibes, disguised as a doctor, drills a hole through the floor of the room above hers, lowers a hose and begins to drip honey over her body. He then pipes locusts through the hole, and when Trout goes to check on the nurse, he discovers that the locusts have devoured her flesh. Because legends state that the death of the first born follows the plague of locusts, Trout fears that Lem may now be in danger and dispatches the police to the Vesalius house, where they discover that Lem has been kidnapped. Phibes then phones Vesalius, stating "the ninth will soon die," and directs him to the dark house on Malden Square, warning him to come alone. When Trout insists on accompanying him, Vesalius knocks him out and hurries to the house. There Phibes informs him that Lem has been locked onto an operating table and the key to the latch has been embedded next to his heart. In six minutes, acid will start to drip onto the table, and unless Vesalius can extract the key and free the boy, his face will be obliterated. To make his point, Phibes rips off his mask, revealing a disfigured, fire-ravaged face. As Phibes plays his organ, Vulnavia, following his orders, takes an axe to the puppet orchestra. Seated at his organ, Phibes descends into his sanctuary just as Trout arrives at the house, and Vesalius extracts the key with only seconds to spare. Vesalius pulls Lem off the table, sending the acid showering onto Vulnavia. Spotting the organ, which has just ascended to the first floor, Trout and the sergeant climb aboard and descend into the sanctuary just as Phibes lies down next to Victoria's embalmed body and seals them into a crypt beneath the floor. When Trout and the sergeant reach the sanctuary, they see no one there.