Donor CD8+ T cells capable of host reactivity inhibit marrow graft rejection, but also generate graft-versus-host disease (GVHD). To evaluate whether the Tc1- and Tc2-type subsets of CD8 cells might inhibit rejection without host reactivity, we established an F1 into-parent murine bone marrow transplant model. Donor Tc1 and Tc2 cells were generated that preferentially secreted type I or type II cytokines; both subsets possessed potent cytolytic function, and clonally deleted host-type allospecific precursor CTL in vitro. B6 hosts receiving 950 cGy irradiation did not reject the donor marrow (F1 chimerism of 78.6%; n = 10), whereas hosts receiving 650 cGy rejected the donor marrow (3.8% chimerism; n = 8). At 650 cGy irradiation, the addition of Tc2 cells to the F1 marrow resulted in extensive F1 chimerism (70.8%) in 8 of 8 recipients; in contrast, alloengraftment was not consistently observed in mice receiving Tc1 cells or unmanipulated CD8 cells. Furthermore, when the preparative regimen was further reduced to 600 cGy, only hosts receiving the Tc2-type cells did not reject the F1 marrow. We conclude that Tc2 cells potently inhibit marrow graft rejection without inducing an alloaggressive response and that non-host-reactive Tc2 cells therefore facilitate engraftment across genetic barriers with reduced GVHD.