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 [3H]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 [3H]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.