We established anti-ganglioside antibody profiles in GBS and studied the frequency, fine specificity and clinical correlate. IgG and IgM antibodies to 8 gangliosides were tested by immunodot-blot in 249 consecutive patients with Guillain-Barré syndrome with large variability in clinical expression, referred to our laboratory over a 8-year period. IgG and IgM anti-GM1 antibodies were measured by Elisa. Thin-layer chromatography overlayed by serum was used to control positivity. 89/249 GBS (36%) had characteristic anti-ganglioside antibody profile. Isotypes were, IgG (62%), IgG + IgM (26%) and IgM (12%). Antecedent infections were found in 62% of GBS included more frequently Campylobacter jejuni and cytomegalovirus. Various autoantibody profiles were described with an immunodominant ganglioside. We detected 6 characteristic anti-ganglioside profiles with fine specificity and immunodominant ganglioside corresponding to 6 immuno-clinical variants of GBS: 1) anti-GM1 and GD1b IgG and IgG > IgM in the acute motor axonal neuropathy after Campylobacter jejuni infection in 41 GBS; 2) anti-GD1a IgG in 6 severe motor axonal GBS after Campylobacter jejuni infection; 3) selectively anti-GQ1b IgG in 17 typical Miller Fisher syndrome with areflexia, ataxia and ophthalmoplegia; 4) anti- GT1b ganglioside and polysialogangliosides IgG (n = 9) in two separate cranial nerve variants, ophthalmoplegic SGB and lower cranial nerve variants depending upon the presenting deficit; 5) anti-GD1b IgG in 5 pure ataxic sensory GBS (4%); 6) anti-GM2 IgM in 11 severe GBS with antecedent CMV infection (8%). 34 GBS (14%) had low levels of anti-GM1 and GD1b IgM antibodies which are not disease specific and may simply represent part of the naturally occurring autoantibody population or a secondary response to disease. 126 GBS (50%) had no antibodies, predominantly in classical form. Associations between isotype, fine specificity and clinical presentation permit the definition of homogeneous immuno-clinical variants. Various autoantibody profiles with diagnostic and prognostic value are easy to perform by immunodot blot in acute peripheral neuropathies.