During a space flight to Saturn, three astronauts are exposed to a blast of radiation which kills two of them and seriously injures the third, Colonel Steve West. He is next shown unconscious in a hospital back on Earth, with bandages covering his face. His physician, Dr. Loring, cannot explain what is happening to West or how he survived the blast. After the doctor leaves, West awakens and is horrified to find the flesh on his face and hands melting away. Hysterical, he attacks and kills a nurse, then escapes the hospital in a panic. Loring and Dr. Theodore "Ted" Nelson, a scientist and friend of West, discover that the nurse's corpse is emitting feeble radiation, and realize West's body has become radioactive. Nelson believes West has gone insane, and concludes he must consume human flesh in order to slow the melting. Nelson calls General Michael Perry, a United States Air Force officer familiar with West's accident, and the general agrees to help Nelson find him.
West attacks and kills a fisherman in a woods, then encounters and frightens a little girl there, but she escapes unharmed. Nelson tracks West by following his radiation trail with a geiger counter, but only finds his detached ear stuck to a tree branch. Perry arrives by plane, and is picked up by Nelson; shortly thereafter, they visit the crime scene where the fisherman's body was found. Sheriff Neil Blake suspects that Nelson knows something, but Nelson tells the sheriff nothing because Perry had earlier informed him that any information about West was classified. Later that night, Nelson returns home to his pregnant wife Judy, who tells him that her elderly mother Helen and Helen's boyfriend Harold are coming over for dinner. On their way, however, Helen and Harold are attacked by West in their car, and he kills them both.
When Blake finds the bodies, he calls Nelson, who comes out to identify them. After Blake angrily demands an explanation, Nelson reluctantly reveals West's condition. Nelson believes West is somehow getting stronger the more his body decomposes. Back at Nelson's house, West attacks and kills Perry, although Judy is not harmed. Nelson and Blake arrive just as West escapes. West then stumbles upon the home of a married couple. West kills the man and attacks his wife, but she drives him away after chopping his arm off with a kitchen knife. Blake receives a call about the attack and takes Nelson with him to investigate. They follow West to a giant power plant, and then up several flights of outside stairways.
Blake tries to shoot West with a shotgun, but the blasts do not stop West, who throws the sheriff over the railing into power lines, killing him. West hits Nelson and knocks him over the railing, leaving the doctor hanging on the side. Nelson appeals to West, reminding him that they were friends, and West decides to pull Nelson to safety. Two armed security guards then arrive and, in a panic, fatally shoot Nelson as he tries to protect West. An infuriated West kills the security guards and stumbles away. After collapsing against the side of a building, he slowly melts completely away. The next morning, a janitor finds his gory remains and casually mops them into a garbage can. The film ends with a radio news report about another astronaut team being sent to Saturn.
- Alex Rebar as Steve West (The Melting Man)
- Burr DeBenning as Dr. Ted Nelson
- Myron Healey as Gen. Perry
- Michael Alldredge as Sheriff Neil Blake
- Ann Sweeny as Judy Nelson
- Lisle Wilson as Dr. Loring
- This was reportedly one of Trace Beaulieu's least favorite movies on the show to date.
- The original design that makeup effects artist Rick Baker intended for The Melting Man was more elaborate than what was actually used in the film: Baker created four distinct stages for West's melting, so that it would be a more gradual process than what we actually saw in the movie. Instead, West goes straight into what Baker intended to be the final stage.
- The film was originally intended to be a parody of sci-fi B-movies, performed in a very straight-faced fashion so as to become a kind of black comedy. During production, the producers decided to attempt to re-shape the movie into an actual horror film by demanding new scenes be shot and integrated into the work that had already been done. For this reason, much of the dialog is purposefully awkward and out of tone with the rest of the movie and many scenes are played for laughs (the nurse being chased in the beginning, the scene with the elderly couple, the awkward "No crackers??", the infamous ending of the melted creature being shoveled into a garbage can, etc.).
- The role of Matt Winters, the man Steve kills after he kills General Perry and leaves Ted's house, is played by Jonathan Demme.