To determine the significance of serum anti-GQ_1b IgG antibody, we studied the disease spectrum associated with this antibody and GQ_1b epitope in the human nervous system. We examined sera from 19 patients with typical Miller Fisher syndrome (MFS), five patients with acute postinfectious ophthalmoplegia without ataxia (atypical MFS), six patients with Guillain-Barré syndrome (GBS) with ophthalmoplegia (GBS-OP[+]), and 23 patients with GBS without ophthalmoplegia (GBS-OP[-]). We also examined sera from 84 patients with other neurologic or non-neurologic disorders and from 16 normal control subjects. Eighteen of the 19 patients with typical MFS, all the patients with atypical MFS, and five of the six patients with GBS-OP(+) had increased anti-GQ_1b IgG activity in ELISA, but none of the patients in the other groups, including GBS-OP(-), had it. All the patients' sera that had anti-GQ_1b IgG antibody showed anti-GT_1a IgG activity. Results of absorption studies suggested that the same antibody reacted with GQ_1b and GT_la. An anti-GQ_1b mouse monoclonal antibody immunostained the paranodal regions of the extramedullary portion of the human oculomotor, trochlear, and abducens nerves. Biochemical analysis showed that the human oculomotor nerve contained a larger amount of GQ_1b than did the ventral and dorsal roots of the spinal cord. We conclude that serum IgG antibody against GQ_1b is very closely associated with acute postinfectious ophthalmoplegia in MFS and GBS.