Transfusion-associated graft vs. host disease (TA-GVHD) is a well-known but rare complication that follows infusion of histo-incompatible lymphoid cells, often seen in individuals with impaired cellular immunity. However, we present here a case report of fatal TA-GVHD in a 'presumed' immunocompetent patient after transfusion of a freshly isolated buffycoat from a relative as part of our protocol to prepare the patient for living-related kidney transplantation. To confirm the diagnosis of TA-GVHD, a polymerase chain reaction was used to detect donor cells in various affected tissues. Furthermore, the immune reactivity of the patient against donor and vice versa was tested on samples taken before transfusion using limiting dilution assays. Our patient received a transfusion with blood from a donor who was homozygous at the human leukocyte antigen (HLA) class I loci. Despite incompatibility for HLA class II, infused donor T lymphocytes were not rejected and became engrafted. The patient did not have cytotoxic T lymphocytes to reject the donor cells. DNA polymorphism studies on several organ biopsies confirmed the presence of infiltrating cells of donor origin. This report illustrates the possibility, in the general patient population, of developing TA-GVHD from whole blood transfusion. In the case of pre-transplant blood transfusion, the patient and donor have to be HLA-typed and special care should be taken in the situation of donor homozygosity for HLA class I, even in the presence of HLA class II incompatibility. Protocols in which donor-specific blood or bone marrow transfusions are given in an attempt to modulate the immune system should exclude these combinations.