Receptor binding sites for the phencyclidine (PCP) analogue, [3H]TCP, have been localized in the rat and guinea pig central nervous systems by in vitro autoradiography. Quantitation of [3H]TCP binding site densities in rat brain reveals highest levels in the forebrain, in particular the strata oriens and radiatum of the hippocampus, the molecular layer of the dentate gyrus and superficial layers of the cerebral cortex. Moderate levels of binding occur in the amygdala, thalamus, anterior olfactory nucleus, external plexiform layer of the olfactory bulb, olfactory tubercle, geniculate nuclei and deep layers of the cortex. Low levels of binding occur throughout most of the septum, diagonal band, hypothalamus, pons-medulla and cerebellum. Spinal cord grey matter also has low levels of binding. Excitotoxin lesions of the hippocampal formation, which destroy the pyramidal and granule cells, reduce the binding of [3H]TCP to strata radiatum and oriens and the molecular layer of the dentate gyrus by 60% suggesting that [3H]TCP labels intrinsic neurons in these regions. Residual binding is probably on afferent terminals. Ibotenic acid lesions of the caudate-putamen reduce [3H]TCP binding by 70%, indicating that binding sites are localized on intrinsic striatal neurons. 6-Hydroxydopamine lesions do not alter [3H]TCP binding levels in the caudate, suggesting the absence of binding sites on dopaminergic terminals in the caudate.