Monoclonal anti-I-Jk antibodies (mAbs) were found to inhibit syngeneic and allogeneic mixed lymphocyte reactions by blocking the responder T cells but not the stimulator cells. Only the responses of H-2k and H-2a strains were inhibited. Three different anti-I-Jk mAbs (1G8, 4B11, and KN34) showed different inhibitory patterns in allogeneic mixed lymphocyte reactions of individual H-2k strains, depending on the H-2 and immunoglobulin heavy chain variable region (IgVH) genes possessed by the stimulator strains. The results indicated that I-J epitopes are involved in the self- and allo-recognition sites of T cells, which are clonally distributed and used to recognize Ia plus IgVH-linked products.