We demonstrated that an IgM M-protein from a patient with motor neuron syndrome had antibody activity against gangliosides GM1, GD1b, and asialo GM1. Studies with a sugar-binding lectin suggested that the epitope in the patient's M-IgM involved the Gal(beta 1-3) GalNAc moiety. Immunohistological techniques demonstrated staining of axons in the lumbar roots, granular cells, and white matter in the cerebellum by the patient's M-IgM. We propose that, in this case, an autoimmune mechanism of motor neuron syndrome associated with a monoclonal protein is most likely.