Since the advent of bone marrow transplantation, a vexing clinical problem is that of acute graft-vs-host disease (GVHD). A less well-recognized disorder is that of GVHD in patients receiving blood products containing immunocompetent lymphocytes. Transfusion-associated (TA)-GVHD has a lower incidence and higher mortality (greater than 90%) than bone marrow transplantation-GVHD and until now has been limited to patients with hereditary or acquired immunologic deficits and to patients immunocompromised by chemotherapy for malignant neoplasms. We presently describe a patient who underwent coronary artery bypass graft surgery and who suffered what we believe was TA-GVHD. This diagnosis is supported by considering the chronology of events (in particular, blood transfusion), clinical features (fever, rash, abnormal results of liver function tests, diarrhea, and pancytopenia), and a skin biopsy specimen that revealed basal cell vacuolation and lymphocyte satellitosis that are considered characteristic for this disorder. We believe TA-GVHD can occur in previously immunocompetent patients who receive transfusions of blood products containing functioning lymphocytes and that this awareness will lead to the discovery of additional cases and a better understanding of this disorder.