PURPOSE OF REVIEW: The aim of this article is to review the experience with α1,3-galactosyltransferase gene-knockout pig organ transplantation into nonhuman primates, and related in-vitro studies. RECENT FINDINGS: Since the first transplants of α1,3-galactosyltransferase gene-knockout pig organs into nonhuman primates were reported in 2005, there has been relatively little further in-vivo experience. This experience has demonstrated, however, the importance of pig non-Galα1,3Gal (Gal) antigens as targets for primate antipig antibodies. Several in-vitro studies have confirmed that, although the incidence and levels of anti-non-Gal antibodies in nonhuman primates and humans are significantly less when compared with total anti-pig antibodies (i.e., anti-Gal + anti-non-Gal), they can result in complement-mediated lysis of α1,3-galactosyltransferase gene-knockout pig cells. The in-vivo experience has also confirmed the importance of an immunosuppressive regimen that prevents an elicited anti-non-Gal antibody response, if acute humoral xenograft rejection is to be prevented. The antigen targets for anti-non-Gal antibodies remain uncertain. Evidence is accumulating that differences in the coagulation-anticoagulation systems between pig and primate result in coagulation dysregulation leading to the development of thrombotic microangiopathy and graft failure. SUMMARY: Although they have provided an advance over wild-type pigs as a source of organs, further genetic modification of α1,3-galactosyltransferase gene-knockout pigs is required to overcome the immune barriers of pig-to-nonhuman primate xenotransplantation. © 2007 Lippincott Williams & Wilkins, Inc.