The locomotor stimulant effects of nicotine and amphetamine appear to be dependent on dopamine transmission in the nucleus accumbens. The present aim was to elucidate the contributions of the accumbens core and medial shell to these effects. In the first experiment, rats received bilateral intra-accumbens infusion of the dopaminergic antagonist eticlopride (or saline) prior to saline or nicotine (0.2 mg/kg s.c.) challenge. Eticlopride inhibited basal and nicotine-induced locomotor activity more effectively when infused into the core (0.0625--0.5 microg/side) than into the medial shell (0.5--1 microg/side). In a second experiment, rats received 6-hydroxydopamine infused into the core or medial shell, and were subsequently tested with saline, nicotine (0.2 mg/kg s.c.) and D-amphetamine (0.75 mg/kg s.c.). Residual dopaminergic innervation was assessed by autoradiographic [(125)I]RTI-55 labelling of the dopamine transporter. [(125)I]RTI-55 labelling in the accumbens core was positively correlated with the locomotor stimulant effects of both nicotine and D-amphetamine. In contrast, [(125)I]RTI-55 labelling in the medial shell was associated negatively with amphetamine-induced activity. Recent evidence suggests that dopamine release in the medial shell may mediate the reinforcing effect of nicotine and D-amphetamine. In contrast, the present findings suggest that dopamine release in the core subregion contributes preferentially to the locomotor stimulant effects of nicotine and D-amphetamine.