A team of men in NBC suits with geiger counters comb a secret military base where the government once conducted nuclear tests. An injured man appears and pleads for help, just before they are attacked by a large man wielding a pickaxe. The men are killed and then chained to the back of a pickup truck, and dragged off.
The film opens near the Yuma Flats base at a gas station run by an elderly man, who for an unexplained reason is searching for someone called Ruby and yelling that he doesn't want to be involved any more. Returning to his home, he finds a holdall containing various personal effects and a human ear.
Ethel Carter (Kathleen Quinlan) and her husband Bob Carter (Ted Levine), a retired police detective, are traveling from Cleveland, Ohio to San Diego, California on their silver wedding anniversary. Also present are their daughter Brenda (Emilie de Ravin), son Bobby (Dan Byrd), eldest daughter Lynn (Vinessa Shaw), her husband Doug (Aaron Stanford), their baby daughter Catherine (Maisie Camilleri Preziosi), and the German Shepherds, Beauty and Beast. While "Big Bob", the father, talks to the gas station manager, we see a mutant—most likely Ruby, who we see wearing a red sweatshirt throughout the movie—grab Bobby's red sweatshirt out of the car and run off. Bobby and Brenda head away from the building and Bobby goes into a nearby Porta-Potty. He is urinating when he sees someone watching him through the window. Panicked, he exits the stall and blames the incident on his sister when in actual fact it was the mutant who stole his red sweatshirt from the car. After believing one of the family has seen the contents of the holdall, the attendant tells Bob of a shortcut through the hills which is actually the secret Yuma Flats base. As they pull away, Bobby inquires the location of his sweatshirt, just now realizing that it is missing.
After driving a few miles along the shortcut, the SUV's tires are punctured by a makeshift spike strip causing the car to crash. Bob walks back to the gas station for a tow truck, and Doug walks the opposite way to get help. Meanwhile, the remaining members of the family are being watched by someone through a pair of binoculars. Beauty runs off into the hills and Bobby chases after her, eventually finding her gutted corpse. Frightened and distraught, Bobby runs off, but slips and falls, knocking himself unconscious. A young female mutant named Ruby comes across him and is intrigued by him. As her brother Goggle chews over the dead dog, Ruby safeguards Bobby from him and watches over him until he comes to.
Later, Bob finally makes it to the station and finds the hysterical gas station attendant, who commits suicide by shooting off the front of his own head with a shotgun. In fear, Bob tries to flee from the scene in his car. As he starts the engine, he is taunted "Daddy...Daddy...Daddy!...Oh daddy" by Papa Jupiter (Billy Drago), the leader of the mutated family, but before Bob can flee, Jupiter attacks Bob and drags him into a mine tunnel with the help of his mutated family members, Lizard (Robert Joy) and Pluto (Michael Bailey Smith).
In the hills, Ruby is about to return Catherine to Doug when Lizard attacks. Doug beats and then shoots Lizard in the chest, neck, and finally the shoulder. Ruby gives Catherine back to Doug, who does not notice Lizard stand up, having survived. Ruby throws herself at Lizard, plunging them over a cliff, stopping Lizard from shooting Doug and Catherine, for he picked up the shotgun after recovering. Bobby and Brenda walk through the ruins of their trailer and find Papa Jupiter still alive, though impaled. Brenda kills Papa Jupiter with a pickaxe to the head. Brenda then spots Doug with Catherine and Beast, and the four are reunited. As they celebrate their victory, a pair of anonymous binoculars watches from the hills.
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