Background: Serum IgM binding to GM1 ganglioside (GM1) is often associated with chronic acquired motor neuropathies. This study compared the frequency and clinical associations of serum IgM binding to a different antigen, a disulphated heparin disaccharide (NS6S), with results of IgM binding to GM1. Methods: Serums and clinical features were retrospectively compared from 75 patients with motor neuropathies and 134 controls with amyotrophic lateral sclerosis (ALS), chronic immune demyelinating polyneuropathy (CIDP) and sensory neuropathies. Clinical correlations of positive IgM anti-GM1 testing found in 27 of 2113 unselected serums were also reviewed. Serum testing for IgM binding to NS6S and GM1 used covalent antigen linkage to ELISA plates. Results: High titre IgM binding to NS6S and GM1 each occurred in 43%, and to one of the two in 64%, of motor neuropathy patients. Motor neuropathy syndromes were present in 25 of 27 patients with high titre serum IgM binding to GM1 in the unselected serums. IgM anti-GM1 or NS6S antibody related motor neuropathy syndromes usually have asymmetric, predominantly distal, upper extremity weakness. Conclusions: IgM binding to NS6S disaccharide is associated with motor neuropathy syndromes and occurs with similar frequency to IgM binding to GM1. Testing for IgM binding to NS6S in addition to GM1 increases the frequency of finding IgM autoantibodies in motor neuropathies from 43% to 64%. High titres of serum IgM binding to GM1, tested with covalent ELISA methodology, have 93% specificity for motor neuropathy syndromes. High titres of serum IgM binding to NS6S have specificity for immune motor neuropathies compared with ALS and CIDP.