In Los Angeles, siblings Ellie (Christina Ricci) and Jimmy (Jesse Eisenberg) come across an accident on Mulholland Drive. As they try to help the woman caught in the wreckage, a ferocious creature attacks them, devouring the woman and scratching the terrified siblings. They slowly discover that the creature was a werewolf and that they have fallen victim to a deadly curse. Now that they have been sliced by the werewolf's claws, they will be transformed into werewolves themselves.