In order to investigate the hypothesis that chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease related to the acute inflammatory form of Guillain-Barre Syndrome (GBS), we studied 40 patients, 40 age and sex matched controls with other forms of peripheral neuropathy (ONP) and 37 controls from the same family or household (FC). We sought antibodies to gangliosides GM1 and LM1 by enzyme linked immunoassay (ELISA) confirmed by immuno-overlay. Only 6 (15%) CIDP patients had IgM antibodies to ganglioside GM1 (GM1) and none had IgG antibodies. We found IgM antibodies to ganglioside LM1 in 2 (5%) and IgG antibodies in 4 (10%) CIDP patients. Antibodies of IgG or IgM class were detected by ELISA to chondroitin sulphate C or sulfatide in up to 7.5% of CIDP patients. There were IgM antibodies in 3 (7.5%) and IgG in 4 (10%) patients against 25, 28 or 36 kD myelin proteins identified by immunoblot. Antibodies to any of these candidate myelin autoantigens were not significantly more frequent in CIDP than FC or ONP controls. Sera from 5 CIDP patients with active disease which subsequently responded to plasma exchange did not induce more demyelination upon intraneural injection into rat sciatic nerve than ONP sera. Serum tumor necrosis factor alpha (TNFalpha) concentrations were not increased in any of the CIDP patients. Serological evidence of Campylobacter jejuni (Cj) infection was present in 4 (10%) CIDP patients. IgM antibodies to cytomegalovirus (CMV) were not detected in any sera. CIDP is not commonly associated with either of these infections or with an antibody-mediated response to any of these glycolipid or myelin autoantigens.