The British-American Rocket Group, headed by Professor Bernard Quatermass, launches its first manned rocket into outer space. Shortly thereafter, all contact is lost with the rocket and its three-man crew: Carroon, Reichenheim and Green. The large rocket later returns to Earth, crashing into an English country field. Quatermass and his assistant Marsh arrive at the scene. With them are the local emergency services, Carroon's wife Judith, Rocket Group physician Dr. Briscoe and Blake, a Ministry official who chides Quatermass repeatedly for launching the rocket without official permission. The rocket's hatch is finally opened, and the space-suited Carroon stumbles out. There is no sign of the other two crew. Carroon is in shock, only able to say the words, "Help me". Inside the rocket, Quatermass and Marsh find only the fastened but completely empty spacesuits of the two missing men.
Carroon is taken to Briscoe's laboratory facility on the grounds that conventional hospitals and doctors would have no idea how to evaluate or treat the world's first returned astronaut, now suffering from some sort of adverse outer space event. Even under Briscoe's attentive care, Carroon remains mute, generally immobile, but alert with eyes that now have a feral and cunning quality. Briscoe discovers an oddly disfigured area on his shoulder and notices changes in his face, suggesting some sort of mutation of the underlying bone structure. Meanwhile, Scotland Yard Inspector Lomax has undertaken investigation of the other two men's disappearance and, having surreptitiously fingerprinted Carroon as a suspect, alerts Quatermass that the prints are like nothing human.
At Judith's insistence that Briscoe is not helping her husband, Quatermass agrees to have Carroon transferred to a regular hospital, under guard. Marsh, meanwhile, has developed the film from the rocket's interior view camera, and Quatermass, Lomax and Briscoe watch it. The crew are seen for a time at their duties, then suddenly, something seems to heavily buffet the ship. After that, there is a nightmarish wavering distortion of the cabin's atmosphere, and the men react as if something frightening, yet not visible, is there with them. One by one they collapse, Carroon being the last.
Quatermass and Briscoe determine from the evidence that something living in outer space has entered the spaceship, dissolved Reichenheim and Green in their sealed spacesuits, and evidently entered Carroon's body, who is now in the process of being transformed by this unknown entity. Not knowing any of this, Carroon's wife, Judith, hires a private investigator, Christie, to break her husband out of the secured hospital. The escape is successful, but not before Carroon smashes a potted cactus in his hospital room, which fuses to his flesh. In the lift he kills Christie and absorbs the life force in his body, leaving a shrivelled husk. Judith quickly discovers what is happening to her husband. Carroon disappears into the London night, leaving her unharmed, but completely traumatized.
Inspector Lomax initiates a manhunt for Carroon, who goes to a nearby chemist's shop and kills the chemist, using his swollen, crusty, cactus-thorn-riddled hand and arm as a cudgel and leaving a twisted, empty man-husk to be found by the police. Quatermass theorizes that Carroon has taken select chemicals to "speed up a change going on inside of him". After hiding on a river barge, Carroon encounters a little girl, leaving her unharmed through sheer force of will. That night he is in the zoo, barely visible amongst some shadowed bushes, now with far less of his human form remaining. In the morning, scattered animal carcasses are found, their life forces having been absorbed, with a slime trail leading away from the zoo. Among the bushes, Quatermass and Briscoe also find a small but living remnant of Carroon, and take it back to their laboratory. Following an examination, Quatermass concludes that some kind of predatory alien life has completely taken over and will eventually release reproduction spores, endangering the entire planet.
The remnant, having now grown much larger, breaks out of its glass cage, but dies of starvation on the floor. On a police tip from a vagrant, Lomax and his men track the Carroon mutation to Westminster Abbey, where it has crawled high up on a metalwork scaffolding. It is now a gigantic shapeless mass of combined animal and plant tissue with eyes, distended nodules, and tentacle-like fronds filled with spores. Quatermass arrives and orders London's electrical power centres be combined and the generated power quickly diverted to the Abbey. Heavy duty electrical cable is run and attached to the bottom of the metal scaffolding. The alien creature is cremated by electrocution before it can release its spores.
The threat eliminated, Quatermass quickly walks out of the Abbey, preoccupied by his thoughts. He ignores all who ask questions. Marsh, his assistant, approaches and asks "What are you going to do?" Never breaking stride, Quatermass offhandedly replies, "I'm going to start again". He leaves Marsh behind, walking off into the dark, and sometime later a second manned rocketship roars into outer space.
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