Police investigate a crime scene and discover that ants have mutated into giant creatures that threaten the human species. Guided by scientists, they work to track them down and destroy them.
In a New Mexico desert police sergeant Ben Peterson (James Whitmore) and his partner find a little girl wandering who does not talk and appears to be in shock. They find a car and a trailer that is badly damaged and has recently spilled blood. They call in detectives and an ambulance. They hear an eerie sound. Ben and his partner go to a local store at night, and they find a bent rifle and the owner dead in the basement. Once again they find sugar, this time with ants in it. Ben leaves for town, and his partner is heard screaming during the sound of shots.
At the station a large foot print has not been identified. Fingerprints identified an FBI agent on vacation. FBI man Robert Graham (James Arness) is called in to the station. The coroner Putnam tells them the store owner’s body had much formic acid.
Dr. Harold Medford (Edmund Gwenn) arrives on a plane with his daughter Pat (Joan Weldon), who is also a doctor. He asks where the first atomic bomb was exploded, and Graham says it was in that area. Dr. Medford uses formic acid to get a reaction from the little girl, who shouts, “Them! Them!”
Ben and Graham take the Medfords to the site, and they find another “gigantic” footprint. Graham wants to know Medford’s theory, but he does not want to risk a nation-wide panic until he is sure. Suddenly Pat sees a giant ant near her and tries to flee. Graham and Ben shoot at it, and Dr. Medford tells them to shoot its antennae. They do, and it dies. Medford says it is an ant caused by mutation from radiation. They kill by injecting formic acid, and they communicate with their own kind.
Dr. Medford and Ben in a helicopter piloted by General O’Brien (Onslow Stevens) look for the nest. Dr. Medford calls Pat by radio and is taught to say, “Over.” In the other helicopter Pat and Graham see a giant ant come out of a hole. They see the human skeletons.
Dr. Medford tells General O’Brien that time is most important. O’Brien suggests bombing the nest. Dr. Medford says they forage at night when it is cool, and he suggests bombing at noon tomorrow. He shows a map of how they tunnel. Dr. Graham suggests heat and then cyanide to kill them.
The next day Ben and General O’Brien fire a bazooka, and Graham and an officer fire another. Ben and Graham in chemical gear go to deposit cyanide in the nest. An ant appears, and they use hand grenades. Pat wants to go in with Graham and Ben. Graham objects, but she persuades him her knowledge is needed. They descend by a rope. They walk past dead ants. An ant pushes through a wall, and they shoot flames to kill it. Pat identifies the queen’s chamber with the eggs. She is afraid that some hatched out alive. She orders them to burn everything there.
Dr. Graham asks if they found ants with wings. He says two of the pods are for winged queens. He tells the general to inform Washington.
At a meeting Ben says that he and Graham kept this secret from their superiors. Dr. Medford narrates a film about ants. He says they can lift twenty times their own weight. The queen loses her wings after the wedding flight to her nest. Ants are the only creature besides man that makes war. He asks them to solve the problem by destroying the queens, or else man may become extinct within a year. Outside a reporter questions a senator who says nothing.
They check for reports on flying saucers. In Brownsville, Texas in a hospital room Graham and Pat interview Alan Crotty (Fess Parker). He says he was flying and saw three flying saucers, but they were shaped like large ants. Pat says they believe him. Crotty says they were heading west. Graham tells his doctor to keep him locked up without visitors.
Dr. Medford says they should search as far as Santa Barbara. They get a report that ants attacked a ship in the Pacific Ocean and sank it. Pat says they are investigating a large sugar theft in Los Angeles. Ben and Graham examine the invaded railroad car and a mangled corpse. Ben says his two children are missing. Graham asks their mother, Mrs. Lodge (Mary Ann Hokanson), where they might have gone. Graham questions two drunks who were arrested and a woman who was speeding. At the hospital Ben and Graham interview Jensen (Olin Howland), who says he saw little airplanes for ants. He says he sees them at night and in the river.
They drive their police car in the Los Angeles River. Graham finds a model airplane and has the mother called. Ben sees tire marks. General O’Brien sees a large ant print. An officer confirms it was their model plane, and he says there are 700 miles of tunnels under the city.
At a press conference General O’Brien proclaims that Los Angeles is under martial law, and no one must be outside at night. He explains about the giant ants and says a queen may have established a nest under Los Angeles.
At night army patrols arrive at the river. Mrs. Lodge arrives in a car, and Ben lets her in. General O’Brien orders the search to begin. Trucks and jeeps carry soldiers. Graham, Pat, and Ben are in army gear, and with Major Kibbee (Sean McClory) they lead the way through the sewers. They stop their motors, and Ben hears tapping. He asks for work lights to be turned on in a construction area and goes in armed with a chemical weapon. Ben calls to the children and hears their response. Ben says he sees two ants and asks for troops. Soldiers go down a manhole. Ben shoots flames and kills two ants. As another advances, he takes the boys out. The ant catches him in its pincers. Graham and soldiers arrive and shoot at the ant, killing it. Graham runs to Ben, who says the kids are okay and dies. Soldiers shoot at ants. Dr. Medford tells them to stop firing and asks if they can use the gas. Part of a tunnel collapses, and they dig. Graham shoots at an ant and is nearly caught before it is killed. Dr. Medford and Pat arrive, and he identifies the new egg chamber. He says they must destroy those young queens to finish the job. Dr. Medford says the atomic bomb opened a new world that no one can predict.
This science fiction mystery reflects the dangerous new era of atomic weapons that could cause mutations. The danger of the human species being destroyed by war is symbolized by the giant ants, the only other species that engages in massive wars. If nuclear weapons are not abolished, mankind faces a dangerous future that could wipe out the human race or poison much of the Earth with radiation that would cause numerous mutations.