Antibodies obtained from the plasma of patients with myasthenia gravis (MG) were found to contain reactivity against both the classic target antigen, the acetylcholine receptor, as well as muscle myosin. This observation was consistent with several previously published reports. However, it was also observed in the present study that much of the dual reactivity contained in MG plasma was due to the ability of individual clonotypic species of anti-receptor antibodies to also bind myosin. Furthermore, the cross-reactivity demonstrated by these antibodies appeared to involve a main immunogenic region of the acetylcholine receptor and an enzymatically important region in the head of the myosin heavy chain. This observation appears to provide new explanations for the epitope-restricted antibody response seen in MG patients.