The autoradiographic distribution of [3H]cyclofoxy (6-deoxy-6 beta-fluoronaltrexone) after in vivo administration or in vitro incubation suggests that it labels mu and kappa opioid receptors. In the rat, the pattern of [3H]cyclofoxy binding is similar to the distribution of mu receptors, however labeling is also present in the neural lobe of the pituitary, the central nucleus of the amygdala and the hypothalamus, areas where kappa receptors outnumber mu receptors. In the guinea pig, [3H]cyclofoxy binding sites are dense in the deep layers of the cortex, an area enriched in kappa receptors. These results are consistent with [3H]cyclofoxy binding to mu and kappa receptors.