The present study investigated the regulation of opioid receptors following chronic repeated cocaine administration. Male Fischer rats were injected with saline or cocaine, 45 mg kg-1 day-1, three times daily at 1 h intervals for 14 days. Using quantitative in vitro autoradiography, the density of kappa receptors was significantly higher in the rostral cingulate cortex, rostral caudate putamen, caudal olfactory tubercle, and ventral tegmental area following cocaine administration. No changes in delta receptor number were detected in any brain region examined. Significant mu receptor upregulation was found in the rostral cingulate cortex, nucleus accumbens, rostral caudate putamen, and basolateral amygdala nucleus of the cocaine-treated animals. These results suggest that enhanced dopaminergic activity can regulate mu and kappa opioid receptors.