This study was undertaken to investigate the role of thymic epithelial (TE) cells in the immunopathology of myasthenia gravis (MG). Seventeen thymuses from patients with MG and six normal thymuses were investigated by light and electron microscopy, using a stereologic method. In the myasthenic thymuses the cortex was markedly reduced, while the medulla was hypertrophied and had numerous germinal centers. A subpopulation of cortical TE cells showed a large fibrillar nucleolus and a decreased number of cytoplasmic dense bodies and cysts, indicating decreased function. Medullary TE cells, on the other hand, showed evidence of increased activity with an enlarged euchromatic nucleus and an increased number of cytoplasmic dense bodies. There was a statistically significant negative correlation between the decrease in size of the thymic cortex and the appearance of medullary germinal centers. A significant correlation was also demonstrated between atrophy of cortical TE cells and depletion of cortical thymocytes. Our study shows that both cortical and medullary TE cells are involved in the pathogenesis of MG but have different roles.