The place conditioning paradigm has proven successful in identifying the neural mechanisms of drug reinforcement. Two classes of drugs, opiates and psychomotor stimulants, have received the most study, and in each case an important role for DA neurons of the mesolimbic system has been established. Moreover, both receptor subtypes, D1 and D2, appear to be involved. Despite this progress, the substrates of drug reward are not completely understood. First, a role for DA has not been established for all stimulants: DA receptor blockade failed to affect conditioned place preferences produced by the stimulants methylphenidate, nomifensine, or bupropion. Second, preliminary evidence suggests that intact serotonergic transmission is important in morphine place conditioning, but a similar consistent finding has not been observed with amphetamine place conditioning. Further study may reveal an interesting dissociation of serotonin's role in the rewarding effects of psychomotor stimulants and opiates. Finally, the role of the opiate receptor subtype kappa is not known; also, the significance of the several anatomical sites that support opiate place conditioning remains unclear.