The present experiment assessed the locomotor response to a low dose (1 mg/kg) of systemic D-amphetamine in rats with cytotoxic lesions of the retrohippocampus (entorhinal and extra-subicular cortices), compared with vehicle-operated shams and unoperated controls. Under spontaneous and saline conditions, both the sham and the lesioned animals were more active than unoperated controls, and they did not differ from each other. Systemic D-amphetamine produced increased locomotion in all groups, but this effect was potentiated in animals with retrohippocampal lesions; two control groups did not differ from each other in their response to the drug. The present results are consistent with the suggestion that cell loss within the retrohippocampal region could affect the functional response of nucleus accumbens to amphetamine. The results are discussed in terms of the interaction between the retrohippocampus and nucleus accumbens in the control of mesolimbic dopamine release and the possible implications for schizophrenia.