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A cross-country road trip takes a dangerous detour when driver-for-hire Sean (Kerr Smith) picks up hitchhiker Nick (Brendan Fehr) and the disoriented Megan (Izabella Miko). Both turn out to be infected by a blood disease thanks to a vampire's bite. At a roadside diner, they encounter a crazed and helpless woman, a recent victim of a vampire feeding, and Sean becomes infected.
Now, the three must race against time to track down and kill the source of the virus if they don't want to become bloodsuckers themselves. The vamp in question is the suave Kit (Johnathon Schaech), who has the usual band of trashy minions.