Transfusion-associated graft-versus-host disease (TA-GVHD) is a devastating immunologic complication of blood transfusion. Patients at highest risk include premature infants and other patients who are immunosuppressed as a result of either congenital or acquired disease or because of the administration of immunosuppressive therapy. An additional high-risk group is immunocompetent patients who are heterozygous at a particular HLA locus and who receive blood from a donor who is homozygous at the same locus. The clinical syndrome consists of fever, skin rash, diarrhea, hepatic dysfunction, and bone marrow aplasia. The outcome is nearly always fatal, despite attempted treatments that have included the use of immunosuppressive agents. Hemorrhage and infection are the most common causes of death. Both humoral and cytotoxic mechanisms have been implicated in the pathophysiology of TA-GVHD. The complication of TA-GVHD can be prevented by the use of irradiated blood components. The use of ultraviolet B light-irradiated blood products and leukoreduction filters are also being investigated as potential preventive treatment modalities.