Serum IgM and IgG autoantibodies against carbohydrate epitopes on glycolipids and glycoproteins have been determined in a series of 112 neuropathies associated with monoclonal IgM (M-IgM) by different immunological techniques. The M-IgM anti-myelin sheath antibodies were determined by indirect immunofluorescence microscopy, the M-IgM anti-myelin associated glycoprotein (MAG) antibodies by western-blot analysis, the M-IgM anti-SGPG and SGLPG antibodies by immunodetection on thin-layer chromatography, the M-IgM anti-ganglioside GM3, GM2, GD3, GM1, GD1a, GD1b, GT1b, GQ1b and anti-sulfatide antibodies by immunodot-blot assay on membrane. Among the 112 M-IgM, 81 had autoantibody activity against nerve glycolipid antigens concentrated in peripheral nerve (72%). M-IgM bound strongly to myelin sheath in 34,5% of cases, to MAG in 38% of cases, to SGPG/SGLPG in 52% of cases, to gangliosides in 21.5% of cases and to sulfatide in 26 % of cases. Six M-IgM autoantibody activity profiles have been described in correlation with distinct clinical syndromes: - the M-IgM autoantibody activity profile against the carbohydrate epitope common to the glycolipids SGPG and SGLPG and myelin associated glycoprotein (MAG) in chronic demyelinating sensitive and sensorimotor peripheral neuropathies (58 patients, 52%); - the M-IgM autoantibody activity profile against immunodominant GM1 in demyelinating pure motor neuropathies (9 patients, 8%); - the M-IgM autoantibody activity profile against immunodominant disialosylgangliosides in chronic demyelinating sensitive ataxic neuropathies (8 patients, 7%); - the M-IgM autoantibody activity profile against immunodominant GM2 in demyelinating motor polyneuropathies (3 patients, 2.5%); - the M-IgM autoantibody activity profile against immunodominant GD1a in pure motor polyneuropathies (2 patients, 2%); - the M-IgM autoantibody activity profile against immunodominant GT1b and polysialosylgangliosides in one acute polyradiculoneuropathy (1%). The M-IgM recognized all gangliosides except GM1 and GM2. The neuropathies associated with IgM monoclonal gammopathy with autoreactive specificity form distinct syndromes. In 27.5% of cases, M-IgM had no identifiable activity autoantibodies.