The Man-Thing is a mindless monster living in the Florida Everglades made up mostly of a shambling mound of plant life, in which there is something that was formerly human. There is something else very strange about Man-Thing... its skin exudes a flammable acid that is activated by the emotion of fear, so that "whatever knows fear burns at the Man-Thing's touch..." Left brainless except for the ability to sense emotion, Man-Thing acts like an emotional mirror, being calm and peaceful around those who are calm, and violent and dangerous around those who fear him.

Real estate tycoon F.A. Schist wants to drain parts of the Everglades to build an airport, which is protested by the local Seminole Indians. As the developer's crewmen delve deeper and deeper into the swamp, one of them shows up dead, leading Schist to blame the tribe. The Seminoles know, however, that there is "something" in the swamp, something that burns those who know fear...