Antibodies to ganglioside GM1 have been associated with Guillain-Barré syndrome. To clarify their role we have studied their frequency, fine specificity and relationship to clinical features in a series of patients with this disease. Antibodies to ganglioside GM1 were identified, by both enzyme-linked immunosorbent assay and binding to thin-layer chromatograms of human brain, in 12 (28.6%) of 42 patients with Guillain-Barré syndrome and in only 1 (2.4%) of 41 normal control subjects (p = 0.002). Eight sera contained IgM antibodies and six sera contained IgG antibodies, including 2 sera which contained both. The fine specificity of the sera varied. Only four of the 12 sera also showed reactivity with ganglioside GD1b and gangliotetraosyl-ceramide (asialo-GM1), consistent with reactivity with the terminal Gal beta 1-3GalNAc disaccharide. Two sera had low titre anti-asialo-GM1 antibodies of a different class to the anti-ganglioside GM1 antibodies. The antibodies in these sera therefore react with a variety of epitopes. There was a strong relationship between the presence of anti-ganglioside GM1 antibodies in the acute stage and prolonged disability, especially if IgG antibodies were present. Seven of 12 patients with anti-ganglioside GM1 antibodies had serological evidence of recent Campylobacter jejuni infection, but antigens from a strain of this bacterium not associated with Guillain-Barré syndrome did not absorb the anti-ganglioside GM1 antibodies.