Just-paroled army ranger Cameron Poe (Nicolas Cage) is headed back to his wife (Monica Potter), but must fly home aboard a prison transport flight dubbed "Jailbird" with some of the worst criminals living. Along with Diamond Dog (Ving Rhames) and Baby-O (Mykelti Williamson), genius serial killer Cyrus "The Virus" Grissom (John Malkovich) unleashes a violent escape plot in mid-flight. Secretly working with U.S. Marshall Vince Larkin (John Cusack), Poe tries to foil Grissom's plan.