Opioid agonists and agonist/antagonists comprise a heterogeneous body of compounds that can be partitioned into at least three groups on the basis of their discriminative stimulus properties in several animal species: (1) stimulus effects similar to those of morphine or fentanyl and blocked completely by low doses of antagonists, such as naloxone and naltrexone; (2) stimulus effects similar to those of ethylketocyclazocine or nalorphine and blocked by higher doses of antagonists; (3) stimulus effects similar to those N-allylnormetazocine or phencyclidine and not blocked by antagonists. This diversity of stimulus properties is consistent with other evidence that multiple populations of receptors mediate the actions of opioids. In man, drugs in group 1 produce subjective effects that are entirely morphine-like and highly reinforcing whereas drugs in groups 2 and 3 produce dysphoric and psychotomimetic subjective effects. Thus, discriminative stimulus properties of opioids appear to reflect drug actions at the neuronal level that are directly relevant to potential for abuse in man.