The effect of pretreatment with cyclosporine A, an immunosuppressant, on the morphine-induced place preference was examined in ddY and mu1 opioid receptor-deficient CXBK mice. Morphine produced a significant preference for the drug-associated place in ddY and CXBK mice. Administration of cyclosporine A alone to ddY and CXBK mice did not result in either preference or aversion for either the drug- or vehicle-associated place. On the other hand, pretreatment with cyclosporine A suppressed the place preference induced by morphine in ddY mice in a dose-dependent manner. However, in CXBK mice, pretreatment with cyclosporine A did not affect the morphine-induced place preference. These results suggest that cyclosporine A suppresses the reinforcing effect induced by morphine, and that this suppression by cyclosporine A may be mediated by mu1 opioid receptors.