Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but well-established fatal complication of blood transfusion. It can occur in immunocompetent patients when they receive transfusions from human leukocyte antigen-haploidentical donors who have lymphocytes with antigens that are not recognized as foreign by the host, but that recognize the host's tissues as foreign. It is generally viewed as a T-cell-mediated process. Graft-induced immune hemolysis or passenger lymphocyte syndrome is a well-described complication of marrow or solid organ transplantation in which immune competent donor B cells produce alloantibodies to recipient red blood cell (RBC) antigens and cause hemolysis of the recipient's RBCs. It is generally considered as a separate process from GVHD, although it could be considered a type of GVHD. Despite the theoretical possibility of both a B-cell and T-cell component to TA-GVHD, detection of a humoral antibody in cases of acute TA-GVHD has not been described. We describe the clinical course and laboratory evaluation of a group A combat trauma patient who was acutely resuscitated with group O fresh whole blood and RBCs and group AB fresh-frozen plasma who experienced the onset of the clinical symptoms of TA-GVHD as well as the onset of hemolysis due to donor-derived anti-A in his plasma 11 days after transfusion.