Acute graft-vs.-host disease (aGVHD), a relatively common complication of allogeneic bone marrow transplantation, is mediated by graft-derived T-lymphocytes that recognize host antigens not expressed by the donor. Clinical manifestations of aGVHD involve the skin, gut, and liver with varying degrees of severity. Strategies for prevention and treatment of aGVHD are reviewed. The assessment of the degree of disparity in the human leukocyte antigen (HLA) type of donor and recipient pairs using refined serologic and molecular biologic testing is necessary for the prevention of severe aGVHD. T-lymphocyte depletion of the bone marrow graft removes the effector cells for aGVHD, but is associated with other transplant related morbidity. Immunosuppressive agents, which are used for prevention, are the basis of treatment for aGVHD. Recently developed techniques for tissue typing may result in the more accurate prediction of aGVHD in donor and recipient pairs. Despite the use of careful donor selection, graft T-lymphocyte depletion, and vigorous prophylactic immunosuppression, aGVHD occurs in a large number of bone marrow transplant patients. Treatment of aGVHD with standard immunosuppressive agents is effective in most cases. Newly developed immunosuppressive agents are being studied for the treatment of aGVHD which responds poorly to therapy. Acute graft-vs.-host disease is responsible for significant morbidity in bone marrow transplant patients. Newer approaches to the prevention and treatment of this disease are currently being evaluated.