The efficacy of immunosuppression including intravenous cyclosporine was assessed in a dog model of total orthotopic small bowel transplantation. Without immunosuppression, allografted animals died before the thirteenth postoperative day. Cyclosporine and prednisone therapy afforded a sixfold increase in survival of allografted animals. Bowel preparation, such as ex-vivo irradiation, treatment of the donor animal with antithymocyte globulin (ATG), or bowel preservation, did not appear to affect survival. However, a preliminary study of combination therapy using azathioprine, ATG, prednisone, and cyclosporine indicated that there were fewer early deaths as compared with other groups. Histologically, allografted bowel showed various degrees of mucosal change to which poorer nutritional aspects were attributed. "Intestinal death" caused by rejection was considered to be the principal cause of death in animals with advanced mucosal changes, in particular those who were long-term survivors. However, other debilitating factors (e.g., superimposed infection, endotoxemia, or possibly graft-versus-host reaction) may be present in nonsurvivors demonstrating fewer pathological changes in the graft.