Sir Geoffrey Radcliffe (Vincent Price) is sentenced to death for the murder of his brother Michael, a crime of which he is innocent. He asks Frank Griffin (John Sutton), the brother of the original Invisible Man, for help. Griffin injects him with the dangerous invisibility drug. Just before his execution, he vanishes from his cell. Griffin turns to trying to undo the drug’s effects, both the invisibility, and the creeping insanity. Many invisible guinea pigs die in this effort.

Detective Sampson (Cecil Kalloway) of Scotland Yard guesses what has happened. He moves heaven and earth to capture Radcliffe, but the Invisible Man runs circles around an army of policemen as he himself figures out the identity of the killer. In the mining company the Radcliffe family owns, an incompetent and drunken goon named Willie Spears (Alan Napier) has been promoted to a position of power since the death of Michael, and Radcliffe is suspicious.

Radcliffe forces Spears’ car off the road and terrifies him in the forest until he reveals the killer’s identity—Richard Cobb (Sir Cedric Hardwicke), Radcliffe’s cousin. Radcliffe visits his fiancée Helen Manson (Nan Grey), and she notices him beginning to succumb to megalomania. As he becomes more insane, we recognize Vincent Price’s unmistakable voice more and more, even though we cannot see him. He kidnaps Richard Cobb and learns for sure that he is guilty, but Cobb escapes and Radcliffe pursues him through the mining company. Radcliffe is shot by police, but Cobb is fatally injured in a coal-dump and confesses before he dies.

Radcliffe’s innocence now proven, he is brought to Griffin, who desperately tries to reverse the effects of the serum so he can treat his wound. He asks the mineworkers for blood transfusion and they all volunteer. It seems that the cure does not work, but the new blood itself reverses the effects of the drug and he gradually becomes visible again and is reunited with Helen in an unexpected happy ending.

The film was directed by Joe May as a sequel to The Invisible Man. There were a number of screenwriters and directors before Joe May was chosen to direct and writers Lester K. Cole and Curt Siodmak got the job. Curt Siodmak (The Wolf Man, Donovan’s Brain, Earth vs. the Flying Saucers, and I walked with a Zombie) was the younger brother of Robert Siodmak (The Killers, Son of Dracula, the Dark Mirror, and The Spiral Staircase). The special features were done by John P. Fulton, Bernard B. Brown, and William Hedgcock, who received Oscar nominations but lost to The Thief of Baghdad. The movie cost $ 230,000 to make but grossed four times that amount.

A search for a young, good-looking man even though he would remain invisible until the last scene turned up Vincent Price, no doubt because he could hold an audience just with his voice. Another advantage was that he could speak German, because the director could not speak English and Price could translate the director’s instructions. Price spent the film covered in bandages or black velvet in front of a black background and only appeared on screen for one minute. Effects artist John Fulton spent fifteen days in post-production, working with his crew on the last day until 4:15 AM. The music was the same as Frank Skinner used for Son of Frankenstein.