In 1967, during the Stanleyville mutinies, a virus called Motaba, which causes a deadly fever, is discovered in the African jungle. To keep the virus a secret, U.S. Army officers Donald McClintock and William Ford destroy the camp where soldiers were infected.
Twenty-eight years later, Colonel Sam Daniels, a USAMRIID virologist, is sent to investigate an outbreak in Zaire. He and his crew—Lieutenant Colonel Casey Schuler and new recruit Major Salt—gather information and return to the United States. Ford, now a brigadier general and Daniels' superior officer, dismisses the latter's fears that the virus will spread.
A white-headed capuchin monkey; that is host to the virus is smuggled into the country. James "Jimbo" Scott, a worker at an animal testing laboratory, is infected when he steals the monkey to sell on the black market. Jimbo takes the monkey to Rudy Alvarez, a pet-store proprietor in the coastal-California village of Cedar Creek. He fails to sell the monkey after it scratches Rudy, who also becomes infected. After releasing the monkey into the woods outside of the nearby community of Palisades, he develops symptoms on a flight to Boston and infects his girlfriend, Alice, at the airport. Their illness is investigated by Dr. Roberta Keough, a CDC scientist and Daniels' ex-wife. Jimbo, Alice, and Rudy die, but Keough determines that no one else in Boston was infected.
A hospital technician in Cedar Creek is infected when he accidentally breaks the vial of Rudy's blood. The virus quickly mutates into a strain capable of spreading like influenza, becoming airborne and causing a number of people to be infected in a movie theater. Daniels flies to Cedar Creek against Ford's orders, joining Keough's team with Schuler and Salt. As they begin a search for the monkey, the Army quarantines the town and imposes martial law. Schuler is infected when his suit tears and Keough accidentally sticks herself with a contaminated needle while treating him.
When Ford provides an experimental serum which cures the original strain, Daniels realizes that his superiors were aware of the virus before the outbreak. Daniels learns about Operation Clean Sweep, a plan for the military to contain the virus by bombing Cedar Creek, incinerating the entire town and its residents, ostensibly to prevent Motaba's expansion to pandemic proportions. However, McClintock, now a major general, plans to use the operation to conceal the mutated virus' existence so the original strain can be preserved for use as a biological weapon.
To prevent Daniels from finding a cure, McClintock orders him arrested for carrying the virus. Daniels escapes before he and Salt fly a helicopter to the ship at sea which carried the monkey. Daniels obtains a picture of the monkey and releases it to the media; a Palisades resident, Mrs. Jeffries, realizes that her daughter Kate has been playing with the monkey (which she named Betsy) and calls the CDC. Daniels and Salt arrive at the Jeffries' house where Salt tranquilizes Betsy after Kate coaxes her out of hiding in the woods nearby. When he learns from Daniels about Betsy's capture, Ford delays the bombing.
On their return flight, Daniels and Salt are chased by McClintock in another helicopter. Salt fires two rockets into the trees to deceive him into thinking that they crashed. Once back in Cedar Creek, Salt mixes Betsy's antibodies with Ford's serum to create an antiserum; although Schuler has died, they save Keough. McClintock returns to base and resumes Operation Clean Sweep, refusing to listen to Ford. Daniels and Salt fly their helicopter directly into the path of the bomber's approach to its target.
With Ford's help, Daniels persuades the bomber's flight crew to detonate the thermobaric bomb over water and spare the town. Before McClintock can order another bombing, Ford relieves him of command and orders his arrest. Daniels and Keough reconcile as Cedar Creek's residents are cured.
