In an attempt to reveal the function sites of substance P (SP) in the central nervous system (CNS), the distribution of SP receptor (SPR) was immunocytochemically investigated in adult rat and compared with that of SP-positive fibers. SPR-like immunoreactivity (LI) was mostly localized to neuronal cell bodies and dendrites. Neurons with intense SPR-LI were distributed densely in the cortical amygdaloid nucleus, hilus of the dentate gyrus, locus ceruleus, rostral half of the ambiguus nucleus, and intermediolateral nucleus of the thoracic cord; moderately in the caudatoputamen, nucleus accumbens, olfactory tubercle, median, pontine, and magnus raphe nuclei, laminae I and III of the caudal subnucleus of the spinal trigeminal nucleus, and lamina I of the spinal cord; and sparsely in the cerebral cortex, basal nucleus of Meynert, claustrum, gigantocellular reticular nucleus, and lobules IX and X of the cerebellar vermis. Neurons with weak to moderate SPR-LI were distributed more widely throughout the CNS. The regional patterns of distribution of SPR-LI were not necessarily the same as those of SP-positive fibers. The entopedunucular nucleus, substantia nigra, and lateral part of the interpeduncular nucleus showed intense SP-LI but displayed almost no SPR-LI. Conversely, the hilus of the dentate gyrus, anterodorsal thalamic nucleus, central nucleus of the inferior colliculus, and dorsal tegmental nucleus showed intense to moderate SPR-LI but contained few axons with SP-LI. These findings confirmed the presence of the "mismatch" problem between SP and SPR localizations. However, the distribution of SPR-LI was quite consistent with that of the SP-binding activity, which has been studied via autoradiography. This indicates that the sites of SPR-LI revealed in the present study represent most, if not all, sites of SP-binding activity.