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Sixty-one evaluable patients, 19 with advanced aplastic anemia and 42 with end stage hematological malignancies, were conditioned for marrow grafting with total body irradiation or cyclophosphamide, or a combination of both. Marrow graft donors were siblings matched at the HL-A region and nonreactive in mixed leukocyte culture. All patients received methotrexate postgrafting to modify anticipated graft-versus-host disease (GVHD). Forty-three of the 61 patients developed clinically recognizable GVHD. In seven GVHD was limited to the skin. In the remaining patients, skin involvement was more severe and was followed by gastrointestinal involvement manifested by anorexia, nausea, diarrhea, abdominal pain, and malabsorption and/or liver involvement manifested by hepatomegaly, rises in serum glutamic oxaloacetic acid transaminase, and bilirubin. The severity of GVHD showed no correlation with the underlying disease, the conditioning regimen, or the day of onset after grafting. Fourteen of 25 patients without GVHD or with only skin involvement are alive. By contrast, only 5 of 36 with severe GVHD are alive. Twenty-six of the 36 patients with severe GVHD succumbed to infection, whereas only 4 of 25 without GVHD or with only skin involvement did so. The results show that despite histocompatibility matching and methotrexate therapy, GVHD remains a serious and often fatal complication of marrow transplantation.