We compared anti-GM1 IgM antibody titers in patients with various neurologic diseases and in normal subjects. We found increased titers in patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without multifocal conduction block. In patients with other diseases, titers are similar to those in normal individuals, suggesting that anti-GM1 antibody levels are not increased nonspecifically after neural injury or inflammatory diseases. Anti-GM1 antibodies in many of the patients occur as monoclonal gammopathies, predominantly of lambda light-chain type, but the antibodies are sometimes polyclonal with normal or increased serum IgM concentrations. Most of the anti-GM1 antibodies appear to react with the Gal(beta 1-3)GalNAc epitope which is shared with asialo-GM1 and GD1b, but in some patients the antibodies are more specific for GM1 and associated with motor neuropathy. Patients with motor or sensorimotor peripheral neuropathy or lower motor neuron disease should be tested for anti-GM1 antibodies or anti-Gal(beta 1-3)GalNAc antibodies, as therapeutic reduction in antibody concentrations was reported to result in clinical improvement in some patients.