One of the first of the "nuclear monster" movies, and the first "big bug" film, Them! was nominated for an Oscar for Special Effects and won a Golden Reel Award for Best Sound Editing. The film starts off as a simple suspense story, with police investigating mysterious disappearances and unexplainable deaths. The giant ants are not even seen until almost a third of the way into the film.
The film begins with New Mexico State Police Sergeant Ben Peterson (James Whitmore) and his patrol partner Ed Blackburn (Chris Drake) discovering a little girl wandering the desert near Alamogordo, mute and in a state of shock. They retrace her steps to a trailer owned by an FBI agent named Ellinson, who was on vacation in the area with his wife and two children. The side of the trailer has been ripped open from the outside, and the parents are missing and presumed dead. The girl briefly responds when strange sounds echo out of the desert wind, but the troopers miss this.
More mysterious deaths and disappearances occur in the area. A general store owner named Gramps Johnson is found dead in his store, which had been literally torn apart. All the money is left in the register, but a barrel of sugar had been smashed open. Gramps' empty rifle has been bent in half. Peterson leaves to check on the status of the little girl, leaving Blackburn to guard Gramps' store. Not long afterward he hears a strange noise outside, pulls his weapon and goes out to investigate. Soon there is the sound of several gunshots, the strange sound gets louder and Blackburn is heard screaming in agony; he has been killed by an unknown assailant.
The police think there is a maniac killer on the loose, but Peterson's boss points out that Gramps' .30-.30 "got off 4 shots" and "Ed Blackburn was a crack shot. He could hit anything he could see. So unless your killer is armored like a battleship, there's no maniac in this case." It's up to the coroner to deliver the verdict that "Gramps Johnson could have died in any one of five ways. His neck and back were broken, his chest was crushed, his skull was fractured and here's one for Sherlock Holmes: there was enough formic acid in him to kill 20 men."
The FBI sends Agent Robert Graham (James Arness) to assist. A single strange track bigger than a mountain lion's is found in the desert near the trailer, and a plaster cast of it is made and sent to Washington, D.C. When the FBI is unable to identify the footprint, it attracts the attention of Harold (Edmund Gwenn) and Pat Medford (Joan Weldon), a father/daughter team of entomologists from the Department of Agriculture.
The elder Dr. Medford arrives on the scene with a theory, but will not disclose it until he tries an experiment on the Ellinson girl. He has her smell the contents of a vial of formic acid, which frees her from her state of near-catatonic withdrawal. She screams "Them! Them!" Medford's theory is validated when the group encounters a giant foraging ant, mutated by atomic radiation to the size of an automobile. The ants produce loud, distinctive stridulating calls that become the iconic signature of the beasts. The lawmen empty their revolvers at the creatures, to little effect. They grab a Thompson submachine gun from the patrol car's trunk and fire it at the monster. They finally kill it by shooting off the creature's antennae, on Medford's advice that ants are helpless without them.
A U.S. Air Force unit is brought in, led by General O'Brien (Onslow Stevens), which locates the ants' nest and exterminates the inhabitants with poison gas. The younger Dr. Medford finds evidence that two young queens have hatched and flown away to establish new colonies. Trying to avoid a general panic, the government covertly investigates any reports of unusual activities or sightings of "flying saucers". One of the queens enters the hold of an ocean-going freighter loaded with sugar, which is then overrun by ants who slaughter the crew. The vessel is subsequently sunk by a U.S. Navy cruiser. Evidence from an alcoholic in a hospital "drunk tank" (who said that he saw giant ants flying around outside his window) and from the dismembered corpse of a man last seen with his two young sons (now missing) leads the investigation to the storm drain system that empties into the Los Angeles River. Due to the significant threat to the City, the U.S. Army declares martial law and prepares for a major assault on the new nest.
During the assault, Peterson finds the two missing boys alive but trapped near the ants' nest. He goes in alone before backup can arrive. He rescues the two boys and kills several threatening ants with his flamethrower. Peterson then leads the two boys back to the pipe through which he came, intending that they all crawl back through it to safety. Peterson is attacked from behind and as he tries to escape, an ant crushes him.
Graham arrives at the scene with reinforcements, and they fight off the swarming ants. Graham rushes to Peterson. Peterson is only able to utter a few last words to Graham, confirming that the boys made it to safety, before he dies of his wounds. Graham is nearly killed himself when a cave-in temporarily cuts him off from the rest of the men; several ants charge him, but he is able to hold them off long enough for the other troops to tunnel through the debris and come to his rescue. The nest's queen and egg chamber are then destroyed with flamethrowers. The senior Dr. Medford issues a grim warning that "the atomic genie has been let out of the bottle," and further horrors may await mankind. He solemnly intones, "When man entered the atomic age, he opened the door to a new world. What we may eventually find in that new world, nobody can predict."