New insights into the mechanisms of hyperacute rejection, endothelial cell activation and accommodation are clarifying the processes that determine the rejection of discordant xenografts. Recent advances include the identification of endothelial cell antigens targeted by human anti-pig antibodies and an increasing understanding of the mechanisms underlying endothelial cell activation. Novel ways to prevent hyperacute rejection, including new therapeutic agents and the use of organs from transgenic animals, are promising to significantly improve the early survival of pig organs transplanted into man. Clinical xenotransplantation has become a realizable goal.