Count Dracula (Carradine) greets the castle's owner, Dr. Franz Edelmann (Onslow Stevens). The Count, who introduces himself as "Baron Latos", explains that he has come to Visaria to find a cure for his vampirism. Dr. Edelmann agrees to help. Together with his assistants, Milizia (Martha O'Driscoll) and the hunchbacked Nina (Poni Adams), he has been working on a mysterious plant, the clavaria formosa, whose spores have the ability to reshape bone. Edelmann explains that he thinks vampirism can be cured by a series of blood transfusions. Dracula agrees to this, and Edelmann uses his own blood for the transfusions.
That night, Lawrence Talbot (Chaney Jr.) arrives at the castle. He demands to see Dr. Edelmann about a cure for his lycanthropy. Talbot is asked to wait. Knowing that the moon is rising, Talbot has himself incarcerated by the police. A crowd of curious villagers gathers outside the police station, led by the suspicious Steinmuhl (Skelton Knaggs). Inspector Holtz (Lionel Atwill) asks Edelmann to see Talbot, and as the full moon rises, they both witness his transformation into the Wolfman. Edelmann and Milizia have him transferred to the castle the next morning. Edelmann tells him that he believes that Talbot's transformations are not triggered by the moonlight, but by pressure on the brain. He believes he can relieve the pressure, but Talbot must wait for him to gather more mold from his spores. Despondent by the thought of becoming the Wolfman again, Talbot says he wants to kill himself and jumps into the ocean. He ends up in a cave below the castle.
Edelmann searches for him and finds that Talbot survived the fall, but has turned into the Wolfman. The Wolfman attacks, but suddenly returns to his human form. In the cave, they find the catatonic Frankenstein monster (Strange), still clutching the skeleton of Dr. Niemann. Humidity in the cave is perfect for propagating the clavaria formosa, and a natural tunnel in the cave connects to a basement of the castle. Dr. Edelmann takes the monster back to his lab, but considers it too dangerous to revive him.
The Count tries to seduce Milizia and make her a vampire, but Milizia wards him off with a cross. Edelmann interrupts to explain that he has found strange antibodies in the Count's blood, requiring another transfusion. Nina begins shadowing Milizia, who is weakened by Dracula's presence; Nina notices that the Count casts no reflection in a mirror. She warns Edelmann of the vampire's danger to Milizia. Edelmann prepares a transfusion that will destroy the vampire. During the procedure, Dracula uses his hypnotic powers to put Edelmann and Nina to sleep; he then reverses the flow of the transfusion, sending his own blood into the Doctor's veins. When they awake, Dracula is carrying Milizia away. They revive Talbot and force Dracula away with a cross. Dracula returns to his coffin as the sun is beginning to rise. Edelmann follows him and drags the open coffin into the sunlight, destroying Dracula.
Edelmann begins to react to Dracula's blood, and becomes evil. He no longer casts a reflection in a mirror. Falling unconscious, he sees strange visions of himself performing unspeakable acts. When he awakens, his face has changed to reflect his evil nature just like in his vision, then he returns to his normal self.
Edelmann performs the operation on Talbot. Afterwards, he transforms again into his evil self and brutally murders his gardener. When the townspeople discover the body, they chase Edelmann, believing him to be Talbot. They follow him to the castle, where Holtz and Steinmuhl interrogate Talbot and Edelmann. Steinmuhl is convinced that Edelmann is the murderer, and assembles a mob to execute him.
Talbot is cured by the operation, but Edelmann again turns into his evil self. He revives the Frankenstein monster, but the monster is very weak. Nina is horrified by Edelmann's transformation, and Edelmann breaks her neck and tosses her body into the cave. Holtz and Steinmuhl lead the townspeople to the castle. The police attack the Frankenstein monster, but the monster subdues them. Edelmann kills Holtz by accidental electrocution. Talbot shoots Edelmann dead. Talbot traps the Frankenstein monster under fallen shelving. A fire breaks out, and the townspeople flee the burning castle. The burning roof collapses on the Frankenstein monster.John Carradine as Count Dracula
Onslow Stevens as Dr. Franz Edelmann
Lon Chaney Jr. as Lawrence "Larry" Talbot / The Wolf Man
Martha O'Driscoll as Milizia Morelle
Jane Adams as Nina, the hunchback
Lionel Atwill as Police Inspector Holtz
Ludwig Stössel as Ziegfried
Glenn Strange as Frankenstein's Monster
Skelton Knaggs as Steinmuhl
Cast notes:Lon Chaney Jr. had played the Wolf Man in all three of Universal's previous films about the character, and Glenn Strange had played the Monster once before, in House of Frankenstein. John Carradine had also played Count Dracula once before, also in House of Frankenstein, and went on to play the part three more times, in Billy the Kid Versus Dracula (1966), Las vampiras (1969), and Nocturna (1979).
House of Dracula was Lon Chaney's last film under contract to Universal, which released him from his contract afterwards, although he returned to play the Wolf Man again in the 1948 comedy Abbott and Costello Meet Frankenstein.
Jane Adams's character, Nina, is a hunchback and was billed as one of the monsters in the film, but in fact, her character is portrayed sympathetically, and the use of an attractive actress to play an otherwise misshapen individual is notable for the time.
Lionel Atwill, familiar to horror movie fans from his performances in 1932's Doctor X, The Vampire Bat, and Mystery of the Wax Museum (both 1933) and many others, was ill during filming of House of Dracula, and died of cancer less than five months after the release of the film.
The working titles for the film were Dracula vs. the Wolf Man or The Wolf Man vs. Dracula.
Although Glenn Strange appears as the Monster in most of the film, footage of Chaney as the Monster from The Ghost of Frankenstein and Boris Karloff from Bride of Frankenstein was recycled; Karloff appears in a dream sequence, while Chaney, as well as his double Eddie Parker, are seen in footage in a fire scene.
Strange recounts that a scene with the Monster stuck in quicksand was particularly arduous for him. On top of three hours of getting into makeup, Strange spent the rest of the day buried in cold sand, including during the lunch break, and was so cold by midafternoon that he could barely feel his legs. Lon Chaney Jr. attempted to help Strange keep warm by passing him a bottle of scotch, with the result that Strange was so drunk that after getting out of costume and makeup, he had difficulty dressing himself in his street clothes. Chaney's drinking contributed to his reputation as being difficult to work with, and probably was the reason Universal let him go after the film was completed.