Intestinal graft-versus-host disease (GVHD) continues to be a significant source of morbidity and mortality after allogeneic stem cell transplantation. Currently, there are no reliable ways to monitor for or predict its occurence before clinical manifestations. Treatment for intestinal GVHD continues to revolve around broad immunosuppression and consequently predisposes patients to signficaint rates of infection. Alpha4beta7 (a4b7) integrin and CCR9 are thought to be two specific mediators of intestinal lymphocyte trafficking, and may present novel targets for the monitoring, prevention, and therapy of intestinal GVHD. Our hypothesis is that a4b7 integrin and CCR9 play essential trafficking roles in the initial allogeneic interaction which leads to intestinal GVHD, and, thus, present novel targets to exploit for monitoring, prevention, and therapeutic applications. Through retrospective and prospective samples, we hope to show that, prior to the onset of actual symptoms, patients have upregulation of both a4b7 integrin and CCR9 expression on subsets of activated T-cells. If this is shown to be true, monitoring these levels may allow pre-emptive therapy to prevent clinically significant morbidity from gut GVHD. In terms of therapy, agents specifically targeted against a4b7 integrin and CCR9, both of which are in development for the treatment of inflammatory bowel disease, will be tested as novel agents for steroid-refractory gut GVHD. The eventual hope will be to include these targeted approaches for prophylaxis as well.