The expression of nerve growth factor (NGF) receptor in adult rat brain was studied by immunohistochemistry with a specific anti-rat NGF receptor monoclonal antibody, 192-IgG. Intense NGF receptor immunoreactivity (NGFRI) was found in structures known to be NGF responsive, including forebrain cholinergic neurons in medial septum, diagonal band of Broca, and basal nucleus of Meynert; central processes of neural-crest-derived sensory ganglion neurons and their innervated nucleus also contained such immunoreactivity. Distinct NGFRI staining was also found in many brain areas and cell types not known to be NGF responsive, including some hypothalamic regions, circumventricular organs, some areas related to the optic system, olfactory glomeruli, ependymal and subependymal cells in some locations, mesencephalic nucleus of the trigeminal nerve, cerebellar molecular layer, central linear nucleus, solitary tract and its nucleus, and inferior olive. The NGFRI in the circumventricular organs was further studied by in vivo labeling of 125I-ligands. Intravenously injected 125I-NGF, but not 125I-cytochrome c, was specifically accumulated in the area postrema. Biochemical study of the NGF receptor showed a major band of molecular weight of approximately 90 KDa in the area postrema, choroid plexus, median eminence, and medial septum with the relative content consistent with that seen by immunohistochemistry. No evidence of a truncated NGF receptor was observed. The results of this study suggest that NGF and its receptor have broader roles in adult mammalian brain than previously thought.