Polyneuropathies associated with IgM monoclonal gammopathy (IgM-MG) are the most frequent types of peripheral neuropathies associated with monoclonal gammopathy. The pathogenic relevance of IgM-MG in peripheral neuropathies is supported by several arguments. The more significant are pathological data on nerve biopsies and the demonstration of IgM antibody activity to peripheral nerve antigens, mainly myelin-associated glycoprotein (MAG) and, sulfated 3-glucuronyl paragloboside (SGPG) and sulfated 3-glucuronyl lactosaminyl paragloboside (SGLPG). The objective of this study was to determine the performance characteristics of 3 immunoassays for detection of anti-myelin antibodies in neuropathy associated with monoclonal IgM gammopathy. Monoclonal IgM may show antibody activity to carbohydrate epitopes shared by several nerve specific antigens. Results obtained with three reliable assay systems, indirect immunofluorescence for antibodies to myelin sheaths (33%), thin layer chromatography for anti-SGPG/SGLPG antibodies (54%) and Western-blot for anti-MAG antibodies (39%). Comparing the different assay systems for carbohydrate structure present on both MAG and SGPG/SGLPG on myelin sheath, the thin layer chromatography appeared to be more sensitive and reliable than Western blot.