An immunological mechanism may be responsible for the peripheral neuropathies related to IgM monoclonal gammopathies. Myelin-associated glycoprotein (MAG) has been found to be one the main target antigens for these paraproteinemias. Glycosphingolipids of peripheral nerve have been also found to be targets for these antibodies, especially a sulfated glycosphingolipid containing glucuronic acid (GLSG) specific for peripheral nerve. Crossed reactivity has been found between MAG and GLSG. Anti-glycolipid antibodies were determined in 14 patients with IgM gammopathy and polyneuropathy. Glycosphingolipids from human peripheral nerve were purified and chromatographed by thin-layer chromatography for immunodetection of the antibodies. The 12 patients who had GLSG antibody activity had a clinical status identical to the reported cases of dysglobulinemic neuropathies with anti-MAG antibodies.