The Carlina Rios, a Brazilian trawler, drifts into the Mississippi River Delta near New Orleans and is accidentally rammed and sunk by the freighter Eastern Hornet. The Coast Guard investigates the wreck but finds no surviving crew members, and the first mate and quartermaster of the Eastern Hornet mysteriously disappear during the incident. Shortly after, people and animals begin turning up dead, their bodies marked by insect sting wounds, and the case widens when the local Sheriff McKew Ben Johnson's dog is found dead, its body bearing the telltale signs of bee stings.
Coroner Dr. Jeff DuRand Michael Parks is called to the scene and makes a startling discovery: the animal’s stomach contains a massive volume of bees. He contacts Jeannie Devereaux Gretchen Corbett, an entomologist and his former girlfriend, to help unravel the mystery. DuRand also warns the police, but the skeptical lieutenant in charge resists any broad warning to the public because Mardi Gras is already underway in the city, and panic could cause more harm than good.
DuRand and Devereaux team up with Dr. Rufus Carter Paul Hecht to investigate. They uncover evidence that the dangerous insects stem from an aborted crossbreeding and import project aimed at boosting honey production in Brazil about a decade earlier. The plan involved introducing a new bee strain, but unchecked crossbreeding with local bees created an extremely aggressive subspecies that reacts strongly to loud noises. Carter cautions that warning the population could trigger unnecessary slaughter of even harmless bees, which would threaten pollination and food production nationwide.
Armed with this alarming insight, DuRand and Devereaux inform Deputy Mayor Pellegrino James Best, who refuses to help, prompting them to seek out Dr. Jorge Mueller Horst Buchholz, one of the scientists behind the project. Mueller’s proposed solution to the swarm is controversial: release a new queen to initiate another round of crossbreeding, which would quell the current aggressive behavior. Killing the existing queen would only scatter the swarm, spreading the danger further rather than containing it. In the meantime, DuRand and Devereaux rekindle their romance as the investigation presses on.
Sheriff McKew mobilizes his deputies into search teams, and the swarm is eventually traced to a snack stand on the outskirts of the city. Mueller bravely enters the hive, but two Mardi Gras revelers crash the checkpoint and stumble into the stand, agitating the bees. In the ensuing chaos, one of the jubilant visitors compromises Mueller’s protective suit, and all three are stung to death. With the danger intensifying, Devereaux’s car is swarmed when she accidentally hits the horn, drawing the bees toward the vehicle.
Carter advises using the car’s momentum to relocate the swarm to a cooling location, where a dramatic drop in ambient temperature can render the bees lethargic. Through coordinated communication via walkie-talkies, DuRand directs Devereaux to the Caesars Superdome while he and McKew clear pedestrians from the route. As they approach the stadium, the bees stall the engine, and a police cruiser is used to nudge the car forward. Inside the playing field, the cooling system is cranked up, gradually freezing the swarm into a harmless state. The relief is tempered by the sight of a lone bee that managed to slip free of the frost, hinting that the threat may not be completely contained.
