Safe and effective xenotransplantation would provide a valuable answer to many of the limitations of allogenic transplantation. Such limitations include scarcity of organ supply and morbidity to donors in cases of living-related donor transplantation. The main hurdle to the efficacious application of xenotransplantation in clinical medicine is the fierce host immune response to xenografts. This immune response is embodied in 3 different types of xenograft rejection. Both hyperacute rejection and delayed xenograft rejection are mediated by natural antibodies and are concerned primarily with whole organ rejection. Cellular xenograft rejection (CXR), on the other hand, is concerned with both whole organ and CXR and is mediated by innate immunity rather than natural antibodies. Macrophages, which are cells of the innate immune system, play a role in all 3 types of xenograft rejection (not just CXR). They impart their effects both directly and through T-cell activation.