Myasthenia gravis (MG) is an autoimmune disease associated with thymic hyperplasia and is much more prevalent in women than men. In this study we investigated potential changes in estrogen receptor (ER) expression in thymic hyperplasia. We first quantified by real-time PCR the relative expression of ER alpha and ER beta in normal thymus and found that the ER beta to ER alpha ratio was inverted in thymocytes (8.6 +/- 1.2), compared with thymic epithelial cells (0.18 +/- 0.05). The ER transcript number gradually decreased in thymic epithelial cells during culture, indicating that the thymic environment influences ER expression. CD4+ helper T cells expressed higher level of ERs, compared with CD8+ cells, as assessed by flow cytometry in thymocytes and peripheral blood mononuclear cells. In MG patients, we found an increased expression of ER alpha on thymocytes and both ERs on T cells from peripheral blood mononuclear cells, indicating that the signals provided by thymic and peripheral microenvironments are distinct. Finally, activation of normal thymocytes by proinflammatory cytokines induced increased expression of ERs especially in the CD4+ subset, suggesting that an excess of proinflammatory cytokines could explain the increase of ERs expression on MG lymphocytes. The dysregulation of ER expression in MG lymphocytes could affect the maintenance of the homeostatic conditions and might influence the progression of the autoimmune response.