Allogeneic peripheral blood stem cell transplantation (PBSCT) is primarily limited by graft-versus-host disease (GVHD). In murine models, we found that donor CD4+ Th1 cells (secretion of IL-2 and IFN-Gamma) mediate GVHD. In contrast, donor Th2 cells (secretion of IL-4 and IL-10) do not generate GVHD, and abrogate Th1-mediated GVHD. We also found that murine allografts enriched with Th2 cells reduced GVHD without impairing the ability of donor T cells to prevent graft rejection. These studies indicate that donor Th2 cells may be a new approach to reducing GVHD.