Three patients with a monoclonal IgM kappa paraproteinemia had a slowly progressive segmental demyelinating peripheral neuropathy. Sural nerve biopsies showed predominantly large fiber loss, with widening of the intraperiod line of myelin associated with active demyelination. Immunoblot analysis showed reactivity of IgM to myelin-associated glycoprotein (MAG) of human myelin. An enzyme-linked immunosorbent assay (ELISA) was developed to provide a simple quantitative technique for detection of antibodies to MAG. Treatment with corticosteroids, immunosuppressive agents, and plasmapheresis produced no significant improvement.