Long-standing rat skin xenografts on immunosuppressed mice are known to become insensitive to destruction by mouse anti-rat serum. Our present experiments demonstrate that long-standing primarily vascularized rat-to-mouse cardiac xenografts, unlike skin, remain fully sensitive to antiserum-mediated destruction, even in mice also bearing a long-standing skin graft that is resistant to antiserum. It appears that skin grafts become resistant to antiserum-mediated destruction because of extensive replacement of the endothelium by cells of host origin. The hearts remain sensitive to anti-serum since such an extensive endothelial replacement would not occur as readily in these whole organ grafts.