Lymph nodes, spleen and thymus obtained from Lewis rats were examined over the course of experimental autoimmune myasthenia gravis (EAMG) for the distribution and the number of antigen-reactive CD4+ T helper cells which, upon recognition of Torpedo acetylcholine receptor (AChR) or the alpha, beta, gamma or delta subunits of Torpedo AChR, responded by secretion of interferon-gamma (IFN-gamma). T cells with these specificities were detected in these three immune organs. Numbers were highest in lymph nodes. In spleen and thymus, numbers of antigen-reactive T cells did not differ. T cells reacting against the intact AChR were more frequent than T cells recognizing any of the subunits. The immunogenicity between the four subunits did not differ, with the exception that the alpha subunit induced a slightly higher T-cell response. No restriction of the T-cell repertoire to the four subunits was detected during early compared to late phases of EAMG. The AChR and subunit-reactive T cells could--via secretion of effector molecules including IFN-gamma--play an important role in the initiation and perpetuation of EAMG, and consequently also of human myasthenia gravis. T cells with the same specificities were also detected in control animals injected with adjuvant only, but at much lower numbers which were within the range of T cells recognizing the control antigen myelin basic protein. They could represent naturally occurring autoimmune T cells.