Graft-versus-host disease (GVHD) represents the major barrier to successful allogeneic bone marrow transplantation. Positive and negative selection studies have unequivocally demonstrated that donor T cells are responsible for the induction phase of GVHD. Inhibition of the early steps of T cell antigen recognition leading to graft-versus-host disease has become an area of intense investigation. Peptides with high binding affinity for class II MHC molecules have been shown to compete for the single class II binding site and to inhibit T cell proliferative responses in vitro. Recent work has extended this approach to the prevention of murine GVHD in vivo.