Serum IgG autoantibodies to GQ1b ganglioside are associated with the acute phase of the Miller-Fisher syndrome (MFS). We investigated the effects of three anti-GQ1b-positive MFS sera in the mouse phrenic-nerve/diaphragm preparation. Miniature endplate potential frequencies increased eight-fold within 25 min, declined rapidly, and ceased altogether after 3 h, when nerve stimulation no longer evoked a response. One MFS convalescent serum (anti-GQ1b negative) and sera from healthy controls and from patients with other neurological diseases were without effect. Thus muscle weakness in MFS may be caused by a serum factor, likely to be GQ1b antibody, that leads to failure of acetylcholine release from motor nerve terminals.