The ␣47 integrin plays a central role in the homing of T cells to the gut. We hypothesized that absence of the 7 subunit would result in a reduction of intestinal graft-versus-host disease (GVHD) and an improvement in overall GVHD morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT). Analysis of alloreactive 7 ؊/؊ T cells showed intact activation, proliferation, cytokine production, and cytotoxicity. However, recipients of 7 ؊/؊ donor T cells in murine HSCT models experienced less GVHD morbidity and mortality than recipients of wild-type (WT) T cells, associated with a decrease in donor T-cell infiltration of the liver and intestine and with an overall significant decrease in hepatic and intestinal GVHD. In graft-versustumor (GVT) experiments, we demonstrated intact or even enhanced GVT activity of 7 ؊/؊ donor T cells. In conclusion,