αB-Crystallin, a small heat shock protein, is an immuno-dominant antigen with increased tissue expression in demyelination. To investigate the humoral response against αB-crystallin, the sera and CSF samples of patients with multiple sclerosis (MS), Guillain-Barré syndrome (GBS), neuro-Behçet's disease (NBD) and other non-inflammatory neurological diseases (NIND) were screened by enzyme-linked immunosorbent assay for anti-αB-crystallin IgG and IgM antibodies. Serum and CSF IgG antibody responses to αB-crystallin were significantly elevated only in NBD patients (serum IgG, NBD 1.29±0.49 vs. NIND 0.95±0.39, P=0.01; CSF IgG, NBD 1.22±0.64 vs. NIND 0.81±0.35, P=0.01). Similarly, high serum IgM antibody titres were also detected in NBD (1.83±0.72 vs. 1.16±0.49, P=0.0005) and in MS (1.57±1.07, P=0.046), whereas elevated CSF IgM responses were observed only in GBS (2.09±1.09 vs. 1.41±0.7, P=0.007). Humoral responses against αB-crystallin are increased in NBD and GBS, which may implicate this central nervous system antigen in the causation and pathogenesis of these inflammatory nervous system disorders. Chemicals/CAS: Autoantibodies; Bacterial Proteins; Chaperonins; Crystallins; heat-shock protein 65, Mycobacterium; Immunoglobulin G; Immunoglobulin M