New Mexico State Police Sergeant Ben Peterson (James Whitmore) and Trooper Ed Blackburn (Chris Drake) discover a little girl in shock wandering the desert near Alamogordo, New Mexico. They retrace her steps to a mobile home owned by an FBI Special Agent named Ellinson on vacation with his family. The trailer side is ripped open from the outside; no trace is found of the rest of the family. Only a single, unidentifiable footprint is left behind. A strange, pulsating high-pitched noise comes on the desert wind, and the little girl briefly reacts to it, but no one around her notices.
A general store owner named "Gramps" Johnson is found dead; his store is also torn apart from the outside, and a barrel of sugar inside was smashed open. Gramps' Winchester rifle was fired and is now twisted out of shape. Peterson leaves to make a report, leaving Blackburn in the store; he hears that strange, pulsating noise again and goes outside to investigate; gunshots are fired, the strange sound grows faster and louder, and Blackburn's scream is heard.
A cast of the footprint is sent to Washington, D.C. Peterson's boss points out that Gramps had time to fire all his ammunition, and Trooper Blackburn was a "crack shot", eliminating the possibility of a homicidal maniac. More puzzling is the coroner's report on Johnson's death: he died from a broken neck, back, skull fracture, crushed abdomen, and "enough formic acid in his body to kill 20 men".
The FBI sends Special Agent Robert Graham (James Arness) to New Mexico to investigate. With him he brings Dr. Harold Medford (Edmund Gwenn) and his daughter Dr. Pat Medford (Joan Weldon), both myrmecologists from the Department of Agriculture. The elder Medford exposes the Ellinson girl to formic acid fumes, which revives her from her catatonic state; she screams, "Them! Them!" His suspicions are validated by her reaction, but he will not reveal his theory prematurely.
At the Ellinson campsite, Pat screams when she encounters a giant, eight-foot long foraging ant. On directions from the elder Medford, Peterson and Graham destroy the ant's antennae, blinding it; they then kill it with their Thompson submachine gun. Medford finally reveals his theory: a colony of giant ants, mutated by radiation from the first atomic bomb test near Alamogordo, is responsible for the killings.
A helicopter search conducted on the orders from General O'Brien, discovers the ants' nest and the skeletal remains of past victims including Blackburn. Cyanide gas bombs are tossed into it, and Graham, Peterson, and Pat descend into the nest to kill any survivors. Deep inside, Pat finds evidence that two queen ants have hatched and have escaped to establish new colonies.
The elder Medford gives a government task force a briefing on ants, as the government covertly investigates all reports of any unusual activity. A report arrives of a private pilot (Fess Parker) who has been committed to a mental hospital after claiming that his aircraft was forced down by UFOs, shaped like giant ants. Next, the Coast Guard receives a report of a giant queen hatching her brood in the hold of a freighter at sea in the Pacific; giant ants attack the ship's crew and there are few survivors. The freighter is later sunk by U. S. Navy gunfire, eliminating one of the queens.
A third report comes in that leads Peterson, Graham, and Major Kibby (Sean McClory) to a rail yard in Los Angeles, where a smashed boxcar has been emptied of 40 tons of sugar. An alcoholic in a hospital "drunk tank" claims to have seen giant ants outside his window. The mutilated body of a father is recovered, but his two young sons with him are still missing. Peterson, Graham, and Kibby find evidence that they were flying a model airplane in the Los Angeles River drainage channel near the hospital. Martial law is declared in Los Angeles, and more troops are assigned to find the new nest in the vast storm drain network under the city.
Peterson finds the two missing boys alive deep inside the drain system, trapped near the ants' nest. He calls for reinforcements and lifts both boys to safety just before being attacked by a giant ant that crushes his lower torso. Graham arrives with reinforcements and kills the ant, as others swarm to protect the nest. Peterson dies from his injuries, Graham at his side. Graham and the soldiers fight off the ants, but a tunnel collapse traps Graham. Several ants charge him, but he is able to hold them off with his submachine gun just long enough for troops to break through the collapse. The queen and her young hatchlings are discovered and quickly destroyed with flame throwers. Dr. Medford offers a philosophic observation: "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".
WHAT HAVE THE TWO QUEEN ANTS ESTABLISHED AFTER HATCHING?
NEW COLONIES