To investigate the role of mu opioid receptors in the reinforcing effects of psychotropic drugs, the voluntary ethanol intake and ethanol- and cocaine-induced conditioned place preference in mu opioid receptor-deficient mice and their wild-type counterpartners was tested. Moreover, dopamine D1 and D2 receptor binding was measured. It was found that ethanol intake was significantly lower in deficient mice. Conditioned place preference in wild-type animals was induced with 5.0 mg/kg cocaine and this dose was ineffective in the knockouts. In this group conditioned place preference occurred after injection of 10.0 mg/kg cocaine. Cocaine induced a similar increase in locomotor activity in both groups of mice. There was no difference in dopamine D1 receptor binding, whereas dopamine D2 receptor binding was significantly lower in the hippocampus of deficient animals. This suggests that interaction between opioid systems and dopaminergic systems may account for the differences in responding to the drugs.