Human antibody responses to foreign organs continue to thwart realization of current xenotransplantation approaches. A report in Science (281:1845–1847, 1998) suggests one potential solution may be to tolerize human B cells by autologous transplant using bone marrow cells displaying the pig hyperacute rejection epitope αGal. After showing that Vero cells transduced with α(1–3)galactosyltransferase (αGT) produce the porcine αGal epitope, John Iacomini and colleagues from Massachusetts General Hospital and the Harvard University Medical School (Cambridge, MA) reconstituted lethally irradiated αGT knockout mice (which normally produce αGal reactive antibodies) with autologous bone marrow cells transduced with or without αGT. Several weeks after reconstitution, sera from control animals reconstituted with syngeneic bone marrow lacking αGT showed stable levels of xenoreactive antibodies, whereas sera from animals reconstituted with αGT-transduced cells showed no xenoreactive antibodies, as detected by ELISA, flow cytometry, and the more sensitive fluorescence-based complement-mediated cytotoxicity assay. Iacomini feels that "being able to reprogram the host immune system via the route of molecular chimerism will have important bearings in the fields of transplantation biology and autoimmune disease." The group is currently testing this approach in a baboon model for xenotransplantation.