Graft failure following transplantation with T cell-depleted bone marrow or with tissue naturally devoid of T cells, such as fetal liver (FL), suggests an important role for T cells in ensuring sustained hematopoietic stem cell engraftment. Whether T cells act by eliminating host residual immune cells—or, alternatively, by helping stem cell growth and differentiation—is still to be determined. The purpose of this study was to analyze the effect of T cell supplementation to the FL graft, using a semiallogeneic murine model where the graft-versus-host reaction is absent. Lethally irradiated C3H/ OuJ mice were grafted with 106FL cells from (C3H/ OuJ×BALB/c) F1hybrid mice, with or without 106isogeneic mature T cells (FL and FL+T groups). Recipient animals were then monitored for survival and for hematologic and immune reconstitution. Eight days postgrafting, the number of multipotent stem cells in the spleen was significantly higher in FL+T as compared with FL recipient mice. Addition of T cells to the FL graft provided a faster recovery of hematological parameters and a significant increase in short-term survival (25.5% 6 weeks of survival in the FL group, as opposed to 55.5% 6 weeks of survival in the FL+T group,P<0.01). By contrast, immunological functions, as assessed by mitogen responses, were quite similar in both groups of animals. Overall a promoting effect of T cells in early stem cell engraftment was clearly demonstrated in this murine model, where GVHR is absent. These results provide in vivo support for a direct T cell effect on hematopoiesis.