The role of multiple opioid receptor types in mediating the motivational properties of opioid agonists and antagonists was investigated by means of a place-preference conditioning procedure. Mu-agonists produced positive reinforcing effects in drug-naive animals whereas kappa agonists and the opioid antagonist, naloxone, were aversive. Chronic infusion of naloxone during conditioning, at a dose sufficient to block mu- but not kappa-receptors, antagonized the effects of both morphine and naloxone. This treatment did not alter the aversion produced by the kappa agonist, U69593. These data demonstrate that opioid reinforcement results from an activation of mu-receptors whereas aversive effects are produced by either an antagonist action at this receptor or an activation of kappa receptors. Such results indicate that mu and kappa opioid systems differentially modulate motivational processes.