Graft-versus-host disease (GVHD) is the primary complication of allogeneic, hemopoietic, stem cell transplantation (HSCT). Murine models suggest that gut toxicity, induced by the intensive chemotherapy preceding hematopoietic stem cell infusion, aggravates systemic GVHD. In HSCT patients gut toxicity correlates with chemotherapy intensity. The present study investigates acute GVHD severity and intestinal toxicity in patients undergoing allogeneic HSCT. In 38 patients intestinal permeability was assessed before and after chemotherapy (on days −1, +4, +7 and +14 as related to the stem cell infusion). Cumulative acute GVHD (days 0–100) and clinical intestinal toxicity (days 0–14) were evaluated in parallel. Patients with mild, acute GVHD (grades 0–I) had better-preserved intestinal barrier function (P=0.04) and less pronounced cumulative clinical intestinal toxicity (P=0.02) compared with patients with more severe acute GVHD (grades II–IV). Gut toxicity predicts acute GVHD severity. Therefore, gut protective strategies may diminish GVHD severity in allogeneic HSCT patients.