The possibility that dopamine may modulate the expression of opioid receptors was investigated by determining the effects of chronic cocaine administration on the density of mu-opioid receptors. Quantitative in vitro autoradiography with the highly selective mu-opioid ligand [H-3]DAMGO was used to measure and localize changes in mu-opioid receptors in the brains of rats administered cocaine or saline three times daily for 14 days. Significant increases in [H-3]DAMGO binding were measured in areas of the cingulate cortex, nucleus accumbens, caudate putamen, and basolateral amygdaloid nucleus of the cocaine-treated animals. These results demonstrate that mu-opioid receptors undergo upregulation in response to chronic cocaine exposure and suggest that dopamine activity can regulate the expression of mu-opioid receptors.