We investigated the heterogeneity of serum antibodies to acetylcholine receptor (AChR) by competition with nine antihuman monoclonal antibodies in a cross-sectional study of 36 patients with myasthenia gravis (MG), and in three who showed clinical improvement associated with decrease in total anti-AChR following immunologic treatment. Two specificities were more prevalent in patients without thymoma, an done of these was more prevalent in cases beginning before age 40. Some specificities were stable during serial studies, whereas other fluctuated. We found evidence of three groups of antibody specificities that had different control mechanisms and may define different regions of the receptor.