We examined the proliferative response of T lymphocytes from thirty-eight patients with Graves' disease (17 untreated thyrotoxic and 30 euthyroid on antithyroid medication) to phytohemagglutinin, anti-CD3 MoAb and phorbol esters, as well as the capacities of these lymphocytes to produce interleukin 2 and the density of interleukin 2 receptors and major histocompatibility class II antigens. We found that the response of T lymphocytes to phytohemagglutinin, anti-CD3 monoclonal antibody and phorbol esters from untreated thyrotoxic Graves' disease was significantly enhanced as compared to treated patients and normal controls. Interleukin 2 production by mitogen-triggered T lymphocytes in both treated and untreated patients with Graves' disease was comparable to that of the control population. Interleukin 2 receptor density was found to be normal, whereas that of human leukocyte antigen-DR was increased in both untreated and treated patients. Following lymphocyte stimulation, there was an increase in human leukocyte antigen-DR and interleukin 2 receptor expression in patients with untreated Graves' disease. Significant correlations were found between thyroid hormone concentration and the proliferative responses to the polyclonal mitogen phytohemagglutinin, anti-CD3 monoclonal antibody and phorbol esters in untreated Graves' patients. Furthermore, during the follow-up of 9 patients, attainment of normal thyroid function after antithyroid treatment was associated with a decrease in and normalization of T-proliferative responses. Our data reveal that active Graves' disease is associated with T cell activation and this is probably related to immunological dysregulation as well as to hyperthyroxinemia.