Neurotrophin-3 (NT-3) mRNA is widely distributed in both the peripheral and central nervous systems but neither the distribution of the native factor nor its physiological function is known. In the present study we produced and characterized an antibody to a synthetic peptide and showed that it specifically recognised endogenous rat and recombinant human NT-3 (rNT-3), but not mouse nerve growth factor and recombinant brain derived-neurotrophic factor. NT-3-like immunoreactivity (NT-3-ir) was detected within the distal tubular cells of the kidney, the zona glomerulosa and reticularis of the adrenal cortex, ganglion cells of the adrenal medulla, red pulp of the spleen, epithelial cells of the intestinal villi and parenchymal cells of the liver. Within peripheral ganglia, NT-3-ir was observed in a subpopulation of large sensory neurons of dorsal root, trigeminal and cochleovestibular ganglia but not in principle neurons of the sympathetic ganglia. These results provide the first evidence for the localization of NT-3-ir and indicate its presence in various peripheral organs and large sensory neurons. We conclude that NT-3 may function outside the nervous system in addition to a neurotrophic role within large sensory neurons.