Expression of major histocompatibility complex (MHC) class 2 molecules on the thyroid follicular cells in human autoimmune thyroid diseases has been reported, and is suggested to play a role in the initiation of the autoimmune responses. Interferon γ is known to induce MHC class 2 molecules on cultured thyrocytes. Therefore, we administered recombinant interferon γ to mice to induce MHC class 2 molecule expression in vivo, and investigated the thyroidal changes following MHC class 2 molecule expression. Recombinant interferon γ3 × 105 U, was administered daily, to mice. MHC class 2 molecules, studied by indirect immunohistochemistry, were expressed on the follicular cells on the 2nd to 4th day after the first interferon γ administration and continued thereafter. Serum T4 and T3 concentrations decreased and anti-thyroglobulin antibodies and anti-microsomal antibodies were detected. Lymphocyte infiltrations were observed in the thyroid glands obtained at 28 days, but they were mild. These results suggest that MHC class 2 molecule expression on thyroid follicular cells induces anti-thyroid antibodies and plays an important role in the initiation of autoimmune thyroiditis. However, the progression of the immune response to thyroiditis with lymphocyte infiltration may require some other factor. This new model of autoimmune thyroid disease in mice might be useful to elucidate the pathogenesis of human autoimmune thyroid diseases.