This study examined the effects of sulpiride, a dopamine D2 receptor antagonist, on morphine rewarding properties and its relation to cyclic AMP levels in brain. The morphine-induced reward in mice was observed in a conditioned place preference test. Cyclic AMP was estimated by radioimmunoassay. The time of staying in morphine pairing compartment and the cAMP levels in brain of mice in the morphine group increased as compared with those in other groups (P < 0.05), but there was no significant difference in the time of staying in morphine pairing compartment and the cAMP levels in brain between the saline group and the sulpiride plus morphine groups (P > 0.05). These suggest that the inhibition of morphine-induced reward by sulpiride be due to the prevention of an increase in cyclic AMP levels in brain.