The chimeric nature of the transplanted liver was first demonstrated in 1969 in long-surviving human recipients of orthotopic hepatic allografts. When liver grafts were obtained from opposite-sex cadaveric donors, karyotyping showed that hepatocytes and endothelium retained donor specificity, while the macrophage system was replaced by recipient cells. Donor cells' fate was unclear, but their presence in recipient blood was confirmed by donor-specific immunoglobulin (Gm) types and red-blood-cell alloantibodies. Davies et al. attributed the secretion of donor HLA class I antigens to transplanted hepatocytes, but these HLA molecules likely originated from bone-marrow-derived macrophages or dendritic cells. Recent studies using anatomical and molecular techniques showed donor cells in clinically stable patients many years after liver replacement. In patients with type IV glycogen storage disease, donor cells acted as enzyme couriers, identified by HLA monoclonal antibodies and PCR in biopsies. Similar findings were observed in rat and mouse bone-marrow transplants, suggesting a similarity between liver and bone-marrow transplantation. This systemic chimerism may explain the liver's resistance to rejection and its tolerogenicity to other donor organs. The chimeric structure of the transplanted liver was thought unique until lymphoid and dendritic cell replacement under FK 506 immunosuppression was identified in intestinal allografts. Donor cells spread through vascular routes to host lymphoid tissues, creating mixed allogeneic chimerism without GVHD. GVHD is a minor issue in human small bowel or multivisceral allotransplantation despite histoincompatible donors and mixed chimerism. Resistance to GVHD is also seen with mixed or xenogeneic chimerism after bone-marrow transplantation, possibly due to reciprocal clonal expansion and deletion. The abundance of lymphoreticular cells in the liver and intestine, plus advances in phenotyping techniques, have contributed to understanding cell migration and repopulation after organ transplantation. Cell migration occurs in all successful transplants, with rapid seeding through the bloodstream. Evidence of donor cell migration from kidney allografts was found in 1962-63, and donor cellular immunity was interpreted as adoptive transfer. The reversal of kidney rejection with immunosuppression was attributed to altered graft antigenicity. Cell migration leads to graft acceptance rather than rejection, depending on immunosuppression, organ immunological substrate, donor-recipient compatibility, and other factors. The fine margin between rejection and acceptance was shown by Armstrong et al., who found an association between dendritic cell replacement and renal allograft survival. Cell migration is an invariable early event in graft acceptance, leading to self-perpetuating changes in the host immune response. The reciprocal clonal deletion process may explain GVHD resistance, with immunosuppressive effects proportional toThe chimeric nature of the transplanted liver was first demonstrated in 1969 in long-surviving human recipients of orthotopic hepatic allografts. When liver grafts were obtained from opposite-sex cadaveric donors, karyotyping showed that hepatocytes and endothelium retained donor specificity, while the macrophage system was replaced by recipient cells. Donor cells' fate was unclear, but their presence in recipient blood was confirmed by donor-specific immunoglobulin (Gm) types and red-blood-cell alloantibodies. Davies et al. attributed the secretion of donor HLA class I antigens to transplanted hepatocytes, but these HLA molecules likely originated from bone-marrow-derived macrophages or dendritic cells. Recent studies using anatomical and molecular techniques showed donor cells in clinically stable patients many years after liver replacement. In patients with type IV glycogen storage disease, donor cells acted as enzyme couriers, identified by HLA monoclonal antibodies and PCR in biopsies. Similar findings were observed in rat and mouse bone-marrow transplants, suggesting a similarity between liver and bone-marrow transplantation. This systemic chimerism may explain the liver's resistance to rejection and its tolerogenicity to other donor organs. The chimeric structure of the transplanted liver was thought unique until lymphoid and dendritic cell replacement under FK 506 immunosuppression was identified in intestinal allografts. Donor cells spread through vascular routes to host lymphoid tissues, creating mixed allogeneic chimerism without GVHD. GVHD is a minor issue in human small bowel or multivisceral allotransplantation despite histoincompatible donors and mixed chimerism. Resistance to GVHD is also seen with mixed or xenogeneic chimerism after bone-marrow transplantation, possibly due to reciprocal clonal expansion and deletion. The abundance of lymphoreticular cells in the liver and intestine, plus advances in phenotyping techniques, have contributed to understanding cell migration and repopulation after organ transplantation. Cell migration occurs in all successful transplants, with rapid seeding through the bloodstream. Evidence of donor cell migration from kidney allografts was found in 1962-63, and donor cellular immunity was interpreted as adoptive transfer. The reversal of kidney rejection with immunosuppression was attributed to altered graft antigenicity. Cell migration leads to graft acceptance rather than rejection, depending on immunosuppression, organ immunological substrate, donor-recipient compatibility, and other factors. The fine margin between rejection and acceptance was shown by Armstrong et al., who found an association between dendritic cell replacement and renal allograft survival. Cell migration is an invariable early event in graft acceptance, leading to self-perpetuating changes in the host immune response. The reciprocal clonal deletion process may explain GVHD resistance, with immunosuppressive effects proportional to