Among patients with chronic idiopathic nonfamilial polyneuropathy studied 3 to 21 years after onset, we identified 11 cases associated with monoclonal gammopathy (MCG) (5 with IgGk, 4 with IgMk, 2 with IgG lambda). The patients, aged 29 to 80 years, presented with sensorimotor polyneuropathy of insidious onset and slow, nonfluctuating progression, delayed motor and sensory nerve conduction, and increased cerebrospinal fluid (CSF) protein. None of the patients in the initial or follow-up study (mean, 9.2 years) had or developed signs of multiple myeloma, malignant plasma cell dyscrasia, macroglobulinemia syndrome, amyloidosis, neoplasia, or other associated illness. The CSF revealed abnormalities of protein electrophoresis or immunoelectrophoresis in 9 of the 11 patients. Three of 5 sural nerve biopsies studied by immunofluorescence demonstrated deposition in nerve fibers of the light chain characteristic of the abnormal circulating immunoglobulin. The findings suggest that these patients form a distinct subset of the dysimmune neuropathies. Although the immunoglobulin deposition and abnormal protein patterns in serum and CSF could be secondary to nerve damage, we propose that an immunopathological mechanism underlies the neuropathy. Immunosuppressants had minimal to marked beneficial effect in 4 of 5 patients, indicating that this polyneuropathy is potentially treatable.