The role of dopamine in the control of hippocampal acetylcholine release was evaluated by using in vivo microdialysis. The effects of the two psychostimulants, cocaine and d-amphetamine, were studied on acetylcholine release in the hippocampus and compared to effects observed in the caudate nucleus. Administration of cocaine (10 and 20 mg/kg i.p.) increased acetylcholine release by 130 and 190% in the hippocampus, whereas in the caudate nucleus the enhancement was 51 and 80% over basal values, respectively. After the injection of d-amphetamine (1 and 2 mg/kg i.p.) the enhancement of acetylcholine release was 110 and 210% in the hippocampus whereas it was 35 and 54%, respectively, in the caudate nucleus. As observed in the caudate nucleus, pretreatment with the dopamine D1 receptor antagonist, SCH 23390, antagonized the cocaine- and amphetamine-induced increase in hippocampal acetylcholine release. These results show that cocaine and d-amphetamine, by increasing dopaminergic transmission, enhance the extracellular concentrations of acetylcholine in both brain areas. The relative enhancement in the hippocampus was far greater than that in the caudate nucleus, suggesting that dopaminergic control of cholinergic function differs in these two brain areas. The results also suggest that endogenous dopamine, by facilitating the release of acetylcholine in the hippocampus, may participate in the regulation of hippocampal cognitive processes.