We investigated serum total interleukin-12 (IL-12) levels in patients with Graves' disease and Hashimoto's thyroiditis. The serum IL-12 levels in Graves' disease were significantly increased in the hyperthyroid state, and were decreased during treatment with methimazole or propylthiouracil in accordance with the decline of free tri-iodothyronine (T(3)) levels, free thyroxine levels and thyroid-binding inhibiting immunoglobulin (TBII) levels. When T(3) was administered orally to normal subjects, serum IL-12 levels were slightly increased. These results suggest that IL-12 might be increased due to prolonged stimulation with thyroid hormone, and thyroid hormone by itself might be a self-perpetuating factor of Graves' disease via increased IL-12 production.