The antigen-specific suppressive T-cell factor of mice, which had previously been shown to be an I region gene product, could effectively suppress the in vitro secondary antibody response of spleen cells from syngeneic or H-2 compatible mouse strains but not that of H-2 incompatible strains. The identities among genes in the left side half (K, I-A, and I-B) of the H-2 complex between the donor and recipient strains were found to be both necessary and sufficient for the induction of suppression. This suggests that the acceptor site for the suppressive T-cell factor is also determined by the gene present in the left side half of the H-2 complex. The cell type which expresses the acceptor site was found to be a subset of T cell. In general, the suppressive T-cell factor obtained from F1 mice could suppress the responses of both parental strains, and the parental factors could suppress the response of F1 mice. The results indicate that both suppressor and acceptor molecules are codominantly expressed on F1 T cells. There were found two types of defects in the expression of suppressor and acceptor molecules among mouse strains: A/J mice could not produce the suppressive T-cell factor despite that they could accept the factor produced by other H-2 compatible mouse strains. In contrast, all the B10 congeneic lines could produce the T-cell factor, but could not accept the factor produced by syngeneic and H-2 compatible non-B10 congeneic lines. The F1 hybrid of A/J and B10. A could both produce and accept the T-cell factor, and thus the expressions of suppressor and acceptor molecules were found to be dominant traits. These results indicate that the antigen-specific T-cell-mediated suppression is regulated by at least two genes both present in the H-2 complex, and that the complementation of these two genes is required for the induction of suppression.