Anti-AChR is heterogeneous within individuals and between individuals. Anti-AChR idiotypes are not shared to any large extent. Ten monoclonal antibodies raised against human AChR: (a) bind to five partially overlapping regions; (b) are not idiotypically identical even within a region; (c) do not all bind to the main immunogenic region; (d) four distinguish between normal and denervated human AChR; (e) can be used to define the antigenic determinants in MG. Antigenic specificities vary in different clinical groups. Antigenic specificities can change during the course of the disease, but some remain relatively constant. Thymus cultures make antibodies with the same specificity as those present in the serum of the individual. All monoclonal antibodies bind to myoid cells of normal and MG thymus. We find no convincing evidence of naturally occurring antiidiotype antibodies in MG sera.