In murine myocarditis, it has been shown that natural killer cells first infiltrate the heart, followed by activated T-cells, which play an important role in the pathogenesis of the myocardial damage. In the same model of acute myocarditis, the repertoire of T-cell receptor (TCR) V beta genes in infiltrating cells in the heart has also been shown to be restricted. To study the nature of T-cell infiltration in more detail, the expression of TCR V alpha genes in infiltrating cells in the heart has been analysed by the polymerase chain reaction (PCR), confirmed by Southern blot hybridization with a C alpha cDNA probe. In contrast to spleen lymphocytes, the repertoire of V alpha gene transcripts in the heart was restricted. Infiltrating cells expressing V alpha 10 were found in five of eight hearts of mice with acute myocarditis and infiltrating cells expressing V alpha 7 and V alpha 3 were found in two of eight and one of eight hearts, respectively. Restricted TCR V alpha as well as V beta repertoires indicate that a specific antigen, in the heart was targeted, presented at the groove of major histocompatibility complex molecules. These findings raise the possibility of specific immunotherapy with synthetic TCR V alpha or V beta peptides to prevent T-cell-mediated myocardial damage in patients with viral myocarditis.