The localization of opiate receptors in the spinal cord and lower medulla has been elucidated by the autoradiographic identification of stereospecific [3H]diprenorphine (a potent opiate antagonist) binding sites. The opiate receptors were higly localized to: layers I (marginal cell zones) and II (substantia gelatinosa) of the dorsal horn of the spinal cord; the substantia gelationsa of the spinal trigeminal nucleus; components of the vagal system, including the vagus nerve, nucleus tractus solitarius, nucleus commissuralis, nucleus intercalatus, nucleus ambiguus and nucleus originis dorsalis vagus; the area postrema. Examination of [3H]etorphine (a potent opiate agonist) binding sites showed the same distribution. We conclude that, in these brain regions, opiate receptors are (1) highly associated with areas receiving small, afferent primary fibers, (2) strategically placed to modulate noxious stimuli as well as explain some visceral side effects of opiate administration.