Objective To investigate the aim antigen coursing the hyperacute rejection of xenotransplantation. Methods Documents about hyperacute rejection in xenotransplantation were reviewed and summarized in detail. Results Pig is thought to be one of the ideal donors of xenotransplantation, but the major obstacle is hyperacute rejection mediated by complement that is activated though human serum. ?-Gal is recognized as the major antigen and its expression is controlled by ?-1,3 galactosyltransferase. Immunoabsorption of pre-exsisted antibody, enzymatic digestion of ?-Gal, knockout ?-GT gene and transgenic technology have been used to solve this problem. Even so, there remain other antigens which can combine with natural antibodies in human serum, such as, 40?10 3 molecule in erythrocyte, 210?10 3, 10 5?10 3 and 50?10 3 antigen in pig embryo brain cell, etc. Conclusion ?-Gal is the major antigen which course the hyperacute rejection. Besides ?-Gal, many nonalpha-gal need further investigation.