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 k 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 k opioid receptors.