Nerve growth factor (NGF) receptors in human sural nerve biopsies were detected immunohistochemically using a monoclonal anti-human NGF receptor antibody. NGF receptors were not visualized within the endoneurium of normal adult nerves but were readily demonstrable within the endoneurium of nerves undergoing active axonal degeneration. Immunostaining of adjacent sections for S-100 beta protein, a specific Schwann cell marker, suggested that Schwann cells expressed the NGF receptors induced by axonal degeneration. Residual Schwann cells in nerves in which axons were completely depleted also expressed NGF receptors. NGF receptors were not detected in relation to thinly myelinated regenerating axons, nor were they detected in the endoneurium of nerves that had undergone segmental demyelination and remyelination. The increased expression of NGF receptors in human axonal neuropathies may contribute to regeneration by NGF-responsive neurons in these disorders.