One line (strain) of mouse has been selectively bred in our laboratory for 15 generations to exhibit a very high sensitivity to levorphanol-induced analgesia on the hot plate assay (HAR or high antinociceptive response line). Concurrently, a second line (LAR or low antinociceptive response line) has been bred in the opposite direction, i.e., to exhibit a very low sensitivity under the same conditions. This has resulted in a 7-fold difference in sensitivity between HAR and LAR mice as a result of changes in gene frequency. Receptor autoradiographic studies with 3H-DAGO were carried out in the central gray to find receptor populations differing greatly in density between HAR and LAR mice to parallel their in vivo sensitivity differences: such receptors would then be implicated in mediating in vivo analgesia. The caudal portions of the dorsal raphe nucleus (DRN) showed 1.5- to 2-fold differences in density of mu sites, while the periaqueductal gray (PAG) showed relatively small differences. These results strongly suggest that mu receptors in a portion of the DRN are involved in mediating analgesia due to systemically administered opioids in this population of mice.