Human thyroglobulin (hTg) and human thyroid peroxidase (hTPO) share common B cell epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis. Furthermore, we have demonstrated a functional common T cell epitope between hTg and hTPO in mice. Four hTg peptides in which 5 amino acid residues were identical to those of hTPO, and one hTPO peptide were prepared. Among these peptides, Tg-P4 (residues 2730-2743) and TPO-P4 (residues 118-131) shared the common T cell epitope and both peptides were highly antigenic. In addition, when the spleen cells from mice immunized with mouse Tg (mTg) were restimulated in vitro by Tg-P4 or TPO-P4, as well as by mTg, these cells transferred thyroiditis to naive recipient mice. These findings indicate that this common T cell epitope is immunogenic and related to the development of murine experimental autoimmune thyroiditis. The common T cell epitope between hTg and hTPO may play a role in the pathogenesis of human autoimmune thyroid disease.