In Evans City, Pennsylvania, a man kills his wife and burns down his farmhouse. Firefighters David and Clank — both Vietnam War veterans — are called to the scene. David's pregnant girlfriend, a nurse named Judy, is called to the office of Dr. Brookmyre, where the two children of the arsonist are being treated for burns.
Heavily armed U.S. troops led by Major Ryder take over Dr. Brookmyre's office. Days earlier, an Army plane carrying a bioweapon had crash-landed near the town, infecting the water supply with a virus code-named "Trixie" which is highly contagious and causes victims to either die or become hysterical and homicidally insane.
Government officials send Colonel Peckem and Dr. Watts, who worked on the creation of the virus, to Evans City to contain the virus and work towards a cure. Martial law is declared in Evans City and a quarantine is placed on the town. Army soldiers forcibly move the townspeople into a high school, rousting many from their homes, and shoot anyone attempting to escape. Bombers armed with nuclear weapons are dispatched to destroy the town if necessary.
David, Judy, Clank, teenager Kathy Fulton and her father Artie, try to find a way to escape the town. After spending the night hiding in a country club, the group attempts to escape through the nearby woods, eluding soldiers both on the ground and in an overhead helicopter. They overpower several soldiers in a house. One of the soldiers discloses what he knows about the virus to David, but when one of the soldiers reaches for his gun, Clank opens fire and kills the soldiers. David confides in Judy what he knows about the virus and tells her that Kathy, Artie, and probably Clank are infected.
After Clank beats him for attempting to have sex with Kathy, Artie hangs himself. Kathy wanders outside and is killed by soldiers. Realizing he is infected, Clank kills several soldiers to give David and Judy time to escape. He is then shot and killed. The next night, Judy, now visibly infected, is killed by armed civilians. Angry and frightened, David surrenders to the military. After being taken into custody, David eventually realizes that he is immune to the virus, but he keeps the knowledge to himself.
Dr. Watts develops a potential cure for the virus. But when he tries to take samples to Peckem and Ryder, he is killed and the samples destroyed in a stampede of infected townspeople breaking free from quarantine. Depressed and distraught by his experiences in Evans City, Colonel Peckem is ordered to relocate to Louisville, where symptoms of the virus have been reported.
