Several lines of evidence have demonstrated the presence of three opioid receptor types in the CNS and periphery. These receptors are referred to as mu, delta and kappa, and have been implicated in a wide variety of functions. The present study examines the localization of the kappa 1 receptor, a region of the receptor that has little homology with mu and delta receptors. Immunohistochemical studies in Zamboni-fixed rat tissue demonstrate immunoreactive perikarya and/or fibers in such regions as the deep layers of the parietal, temporal and occipital cortex, parasubiculum, central and medial amygdala, bed nucleus stria terminalis, nucleus accumbens, olfactory tubercle, endopiriform nucleus, claustrum, hypothalamic nuclei, median eminence, midline thalamic nuclei, zona incerta, central gray, caudal linear and dorsal raphe, substantia nigra, pars reticulata, ventral tegmental area, parabrachial nucleus, spinal trigeminal nucleus, nucleus of the solitary tract, spinal cord and the dorsal root ganglia. Specific kappa 1 receptor-like immunohistochemical staining is also observed in the pituitary, where immunoreactive perikarya and fibers are localized in the neural and intermediate lobes. Transfection and preabsorption controls suggest that the antibody is selective for the cloned kappa 1 receptor, and does not recognize mu or delta. This immunohistochemical localization corresponds well to previously described kappa 1 receptor mRNA and binding distributions and provides new insights into the cellular localization and pre- and postsynaptic organization of the kappa 1 receptor-like proteins in the rat brain and pituitary. The functional implications of these results are discussed in light of the kappa 1 receptors play in hormonal regulation, antinociception and reward.