Unresponsiveness to Hh incompatible bone marrow grafts was induced in mice by single or multiple injections of various tissues from a prospective donor before irradiation and bone marrow grafting. The results show that lymph node cells and splenocytes (both adherent and nonadherent) were the most effective in inducing unresponsiveness; thymocytes showed only a marginal effect in female and no effect in male mice, and hepatocytes had no effect. There was a direct relationship between the number of cells required for unresponsiveness induction and the strength of incompatibility between donor and recipient, i.e., the stronger the donor-recipient incompatibility, the more cells were required to induce unresponsiveness. The rapidity of unresponsiveness induction and its duration were also dependent on the number of cells in the "immunizing" inoculum. In general, unresponsiveness was induced sooner and persisted longer when larger cell doses were used. The unresponsiveness was highly specific with regard to donor antigens.