Ten monoclonal anti-human acetylcholine receptor (AChR) monoclonal antibodies (m.abs) all exhibited high avidity binding to the human AChR. None was able to inhibit alpha-bungarotoxin (alpha-Butx) binding to the receptor. Five distinct but partially overlapping antibody-binding regions were defined by competition experiments. Four antibodies, which competed with each other for one region on denervated human AChR and also bound to human fetal AChR, failed to bind appreciably to normal human AChR in solution, to normal AChR solubilized from 6 other species, or to human endplates in frozen sections.