Blood transfusions are known to improve allograft survival times, and this effect is enhanced with recipient immunosuppression. The focus of the present study was to determine the effect of pretransplant and perioperative donor-specific (DST) or nonspecific (NST) blood transfusion on skin allograft survival in thermally injured mice. Allogeneic immune responsiveness was suppressed in 20% TBSA burned mice, but not to a degree which was protective against DST-induced sensitization. Pretransplant DST resulted in accelerated graft rejection in burned recipients, although high-dose cyclosporine partially reversed this sensitization. Additionally, burn-related immunosuppression in this model did not enhance perioperative transfusion-induced graft prolongation. However, when burn-injured perioperatively transfused mice were further immunosuppressed with cyclosporine, significant graft prolongation occurred. These data suggest that perioperative NST may contribute to prolonged skin graft survival in burned recipients, provided that the mice are sufficiently immunosuppressed.