The serum of a 4-year-old child with severe hypertrophic peripheral neuropathy contained high-titer polyclonal antibodies, mainly of IgG class, reacting with the 30-kd Po glycoprotein of peripheral nerve. This was demonstrated by indirect immunofluorescence, immunoblot analysis of myelin proteins, and enzyme-linked immunosorbent assay with purified Po glycoprotein. The antibodies did not react with myelin-associated glycoprotein, sulfated glycuronic acid-containing paraglo-boside (SGPG and SGLPG), or other peripheral nerve glycolipids or gangliosides. To our knowledge this is the first report of strong antibody activity specifically directed against Po. This antibody may play a causative role in the pathogenesis of the peripheral neuropathy in this patient.