In order to investigate the relative contribution of dopaminergic projections to the nucleus accumbens and prefrontal cortex in the regulation of spontaneous and drug-induced locomotor activity, separate groups of rats were prepared with 6-OHDA lesions of the ventral tegmental area alone, or additional grafts of dopamine-rich tissue reinnervating either the nucleus accumbens or medial prefrontal cortex. A fourth unoperated group served as normal controls. The lesions induced no change in spontaneous, daytime activity, but increased overnight activity. The lesioned rats were also hyperactive to apomorphine, while the activational effects of amphetamine were blocked. Grafts of dopamine-rich tissue, whether into the prefrontal cortex or nucleus accumbens, resulted in a significant normalization of both drug responses towards control levels. Neither graft influenced overnight hyperactivity, whereas spontaneous daytime activity was increased above both control and lesion levels by the accumbens grafts alone. The results are interpreted as suggesting that dopaminergic projections to prefrontal cortex and nucleus accumbens are similarly rather than antagonistically involved in the regulation of drug-induced locomotor activation.