On the basis of our experience with rat small bowel transplantation (SBT), we established a model of orthotopic SBT in mice. The immediate success rate was approximately 50%. Indefinite survival was obtained in the syngeneic group. The effect of different immunosuppressive treatments was also investigated: mean survival was 10.2+/-1.2 days in untreated mice receiving allogeneic grafts, 14.2+/-1.6 days with cyclosporine, 24+/-5.1 days in the rapamycin group, and 73.6+/-29.1 days with tacrolimus-treated animals. From this study, we conclude that although the model is technically difficult, it may provide an excellent tool to further investigate the physiology and immunology of small-intestinal transplantation.