CD4+ T cells were cultured from posttransplant cardiac biopsies placed on irradiated feeder cells of autologous cloned donor major histocompatibility complex class II-specific T-cell lines cultured and grown from previous biopsies. Fourteen of the CD4+ T-cell cultures were expanded and cloned using the same feeder cells. Two of the 14 cloned T-cell lines were examined in detail for their ability to proliferate in vitro. Clones 7E4 and 8G2 proliferated (as determined by primed lymphocyte testing) only when cocultured with a series of distinct autologous cloned T-cell lines from previous biopsies that were specific for donor-specific HLA-DR3 and HLA-DR4, respectively. In addition, when HLA-DR-specific T-cell lines were established using recipient peripheral blood mononuclear cells and a series of HLA-DR-expressing homozygous typing cells, clone 7E4 only responded to the series of distinct HLA-DR3-specific autologous cloned T-cell lines but not to autologous HLA-DR2 and -DR4, and clone 8G2 responded to 3 of 8 distinct autologous HLA-DR4-specific T-cell lines, but not HLA-DR2-specific T-cell lines. These data demonstrate that cardiac biopsies contain CD4+ T cells of recipient origin which show anti-idiotype-like reactivity against T-cell receptors specific for donor-specific major histocompatibility complex class II molecules.