Anti‐GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain–Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti‐GQ1b–positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of α‐latrotoxin (α‐LTx) and are induced by antibody‐mediated activation of complement. We developed an assay for detection of the α‐LTx–like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti‐ganglioside antibodies, micro‐electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti‐GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c‐deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross‐reactivity to related gangliosides) are responsible for the α‐LTx–like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002