The authors describe a xenograft model created by interposing human ath erosclerotic tissue into the rabbit aorta. Human atherosclerotic tissue obtained from either peripheral vascular operative specimens or from resected hearts of patients undergoing orthotopic cardiac transplantation were sectioned into 10 patches and 5 vessel segments and placed into the aortas of 15 rabbits. A thin platelet-fibrin layer adhered to the luminal surface of the graft but did not progress to occlude the graft. This layer matured over a two-week period, with ingrowth of fibroblasts. Endothelialization occurred only at the anastomotic sites. Rejection was characterized by development over a ten-day period of mul tinucleate giant foreign body cells and a dense inflammatory infiltrate advanc ing from the adventital surface. No necrosis of the xenograft was evident. This model is applicable to study the effects of balloon angioplasty, "hot tip" devices, mechanical atherectomy instruments, and various laser systems on human cal cific atherosclerotic vessels. Currently available animal atherosclerosis models do not provide a comparable test system.