Antibodies directed against ganglioside GM1 or sulfatides are frequently associated with motor or sensorimotor neuropathies. To establish the prevalence of such anti-glycosphingolipid autoantibodies in autoimmune disorders and to determine whether they contribute to neurologic symptoms in those individuals, we measured these antibodies by enzyme-linked immunosorbent assay (ELISA) in serum samples from rheumatologic patients with and without peripheral neuropathies (PN). We tested 21 patients with systemic lupus erythematosus (9 with PN), 26 with Sjögren's syndrome (12 with PN), 34 with scleroderma (28 with PN), and 14 with rheumatoid arthritis (4 with PN). Samples from 32 normal individuals were also tested. Patients with systemic lupus erythematosus and rheumatoid arthritis had elevated concentrations of GM1 antibodies and scleroderma patients had lower levels of sulfatide antibodies compared to healthy individuals. The presence of ganglioside or sulfatide antibodies did not correlate with the development of peripheral neuropathy in these patients. These findings suggest that relatively low-titer glycosphingolipid antibodies may arise as part of a nonspecific polyclonal gammopathy in rheumatologic disorders but generally without clinical manifestation.