There is increasing evidence that multifocal motor neuropathy (MMN) and some lower motor neuron (LMN) syndromes are immune-mediated and treatable. The frequent occurrence of high titers of anti-GM1 antibodies in these motor neuropathies raised hopes that serum testing would provide useful diagnostic information. Unfortunately, in routine practice, simple quantification of IgM binding to GM1 ganglioside has proved to be a test with poor sensitivity and specificity. We have found that much greater sensitivity and specificity for MMN and LMN syndromes can be obtained by determining serum antibody binding to panels of antigens, such as GM1, histone H3, and NP-9. These results suggest that combined measurement of serum antibody binding to GM1 and other antigens can provide tests that are useful in the diagnosis and management of motor neuropathy syndromes.