To study the role of antigen-specific T lymphocytes in the pathogenesis of autoimmune hepatitis, messenger RNA of T-cell receptors (TCR) was analyzed in liver biopsy specimens from four patients with autoimmune hepatitis. Using the TCR P-chain variable region family specific oligonucleotides, a remarkable bias for the usage of P-chain variable region 3 was detected in all four patients. Therefore, nucleotide and amino acid sequences of the complementarity-determining region 3 rearranged to the P-chain variable region 3, which is a putative contact site for peptide fragments from antigens bound in the groove of the human leukocyte antigen molecule, was further analyzed in randomly selected 10 clones from each patient. An Asp-Arg-Pro motif in the complementarity-determining region 3 was identified in three of four patients with human leukocyte antigen DR4, and this motif was always rearranged to the Pchain junctional region 1.2. From these results, P-chain variable region 3+, Asp-Arg-Pro', P-chain junctional region 1.2+ T-cell clones may be among the responsible lymphocytes involved in the liver damage in autoimmune hepatitis, especially in patients with human leukocyte antigen DR4. Thus, an analysis of the complementarity-determining region 3 may give us an important clue to clarify characteristics of target antigens included in autoimmune hepatitis. (HEPATOLOGY 1995; 22:142-147.) The T-cell receptor (TCR) is a heterodimer composed of a and ,6 chains, or y and 6 chains and is present on the surface of most T cells. This molecule is responsible for recognizing antigenic peptide fragments bound to proteins of the major histocompatibility complex.