Monoclonal proteins (IgM, IgG, and IgA) in the serum or urine of patients with neuropathy may provide a marker for amyloidosis, myeloma, lymphoma, leukemia, Waldenström's macroglobulinemia, or monoclonal gammopathy of undetermined significance (MGUS). The clinical characteristics, course, and electromyographic features among neuropathies associated with monoclonal IgM (IgM-MGUS, 31 patients), monoclonal IgG (IgG-MGUS, 24 patients), and monoclonal IgA (IgA-MGUS, 10 patients) evaluated between 1980 and 1986 were compared. Four statistically significant differences set IgM-MGUS neuropathies apart from IgG-MGUS and IgA-MGUS neuropathies: (1) higher frequency of sensory loss and ataxia, (2) higher frequency of nerve conduction abnormality—10 attributes were significantly worse (none were significantly better), (3) higher frequency of dispersion of the compound muscle action potential, and (4) higher frequency of IgM-MGUS in the MGUS neuropathy cohort than is characteristic of MGUS without neuropathy seen at our institution or than is encountered in epidemiological surveys. These differences were not thought to be due to selection or severity biases. Neither the amount of IgM nor the estimated size of the monoclonal peak was associated with severity of neuropathy. The type and severity of IgM-MGUS neuropathies with anti-myelin-associated glycoprotein antibodies were not significantly different from those without anti-myelin-associated glycoprotein antibodies. A simple relationship between the presence and amount of IgM-MGUS or anti-myelin-associated glycoprotein antibodies and neuropathy cannot be assumed.