We investigated the immunohistochemical localization of α- and β-synuclein (αS and βS) in the adult rat CNS and compared the distribution of these proteins with that of synaptophysin (SYN), a well-established presynaptic marker. Anti-SYN, αS and βS antibodies immunolabeled the neuropil in a punctate pattern. No SYN immunoreactivity was found in the neuronal cytoplasm. In contrast, both anti-αS and βS immunostained the neuronal cytoplasm and nucleus to various extents depending on the brain region. αS-positive neurons were found in the olfactory bulb, deeper layers of the cerebral neocortex, substantia nigra and pontine nucleus. Immunoreactivity was most intense in neurons of the substantia nigra. βS-positive neurons were more widely distributed throughout the CNS: more than 50% of neurons were positive for βS in the granular cell layer of the olfactory bulb, layer IV of the cerebral cortex, CA3 of the hippocampus, basal ganglia and thalamic reticular nuclei. Moreover, there were differences among these proteins in the distribution pattern of immunoreactivity in the neuropil in some CNS regions. These findings suggest that although αS and βS are concentrated in presynaptic terminals, significant amounts of these proteins are also present in the neuronal perikarya. Furthermore, the distribution of αS-positive neurons is similar to that of intraneuronal inclusions in αS transgenic animals as well as in human α-synucleinopathies.