In 1996, a deadly virus believed to be released by Twelve Monkeys wipes out most of humanity. Survivors live underground in 2035 while animals roam. James, a prisoner, is chosen to wear a hazmat suit, gather bug samples on the surface, and return to aid in creating a vaccine. In a failed attempt to travel back in time, mentally unstable James ends up in 1990 chained in a mental asylum. Despite skepticism, he vows to prevent the virus outbreak. The Scientists doubt him until a failed phone call reveals the truth about the time discrepancy. James dreams of the airport amidst the chaos.