The immunology, pathophysiology, incidence, clinical manifestations, grading, and prevention of acute graft-versus-host disease (GVHD) are reviewed. GVHD occurs after allogeneic marrow transplantation when immunologically competent T lymphocytes in the donor marrow identify the host's antigens as foreign and attempt to reject host tissues. Acute GVHD occurs within three months after marrow transplantation and may affect the skin, gastrointestinal tract, liver, and immune system. Even with prophylactic immunosuppression, acute GVHD occurs in 20% to 80% of patients. Moderate to severe GVHD (grades II-IV) is a major cause of morbidity and mortality after allogeneic bone marrow transplantation. Conventional GVHD prophylaxis consists of immunosuppressives such as corticosteroids, methotrexate, and cyclosporine. Methotrexate and cyclosporine are equally effective in preventing GVHD. A combination of both drugs is better than either drug alone and results in an improved survival rate. The addition of corticosteroids to methotrexate, cyclosporine, or antithymocyte globulin is also more effective than single-drug therapy. Serial administration of intravenous immune globulin may contribute additional protection against acute GVHD. There is conflicting evidence concerning the prophylactic efficacy of pentoxifylline. Elimination of T lymphocytes from the donor marrow before transplantation has been associated with less GVHD but a higher incidence of graft failure. Total elimination of GVHD in patients with leukemia may cause loss of a graft-versus-leukemia effect, resulting in increased relapse rates and decreased long-term survival. Promising experimental prophylactic agents include thalidomide, zolimomab aritox, tacrolimus, antibodies to cytokines involved in the pathogenesis of GVHD, and monoclonal antibodies against cytokine receptors on T lymphocytes. Current research efforts are also directed toward eliminating GVHD without compromising the graft-versus-leukemia effect.