The administration of amphetamine to rats results in a relatively wide range of individual differences in responsiveness, both in the initial behavioral patterns as well as in the augmentation response to repeated administration. Therefore we examined the possibility that such differences might reflect intrinsic variation in neurochemical mechanisms regulating responsiveness to amphetamine. Animals were administered a transitional dose (1.75 mg/kg) of amphetamine with regard to the induction of locomotion and continuous stereotypy. On the basis of individual response profiles animals could be separated into two markedly different subgroups, one displaying continuous locomotion (S1), characteristic of lower amphetamine doses, and the other exhibiting a multiphasic pattern, including a prolonged focused stereotypy phase (S2), typically associated with higher amphetamine doses. Examination of regional brain monoamine and metabolite levels revealed distinguishing patterns between the subgroups only in the mesolimbic and mesocortical dopamine systems. With repeated amphetamine administration, the two prominent factors of the augmentation, the emergence of stereotypy and the enhancement of locomotion during the last half of the response, were dissociable between the subgroups. The emergence of stereotypy was confined to S1 animals, whereas only the S2 subgroup displayed the progressive increase in locomotion. Differences in the responsiveness of neurochemical systems to amphetamine rather than pharmacokinetic factors appear to underly the distinct behavioral profiles associated with the two subgroups. The results indicate that characterization of individual responses may be required to determine accurately the neurochemical mechanisms involved in the behavioral effects of amphetamine.