The present study examined the hypothesis that mu-opioid receptors contribute to a behavioral stimulation produced by stimulation of dopamine receptors by comparing responses in mu-opioid receptor knockout and wild type mice. Apomorphine-induced climbing behavior was augmented by 65%, in wild type mice, but not in mu-knockout, following subcutaneous administration of morphine (15 mg/kg). Moreover, pretreatment with either naloxone (an opioid receptor antagonist) or haloperidol (a mixed D(1)/D(2) receptor antagonist) eliminated the enhancement by morphine of climbing behavior in wild type mice. These results indicate that expression of mu-opioid receptors plays an important role in the enhancement of climbing behavior induced by the dopamine receptor agonist, apomorphine. Furthermore, this augmentation is mediated by interaction between dopamine and mu-opioid receptors.