Adult intestinal allografts have demonstrated high immunogenicity in human transplantation, making the search for new and more favorable grafts an actual problem. Accepting that fetal and newborn immune systems are relatively immature, their intestines could be ideal sources for organ donation. The purpose of this study was to compare the immunogenicity of fetal, newborn, and adult intestine for selection of the least antigenic. Using a bidirectional rat model for immunologic responses, 116 small-bowel transplantations were done: 36 fetal, 40 newborn, and 40 adult grafts. Two histocompatibility barriers and different immunosuppression regimes were used. For fetal and newborn intestines, free grafts into the omentum of adult recipients were done; for adult intestines, accessory grafts in adult recipients of the same age, using vascular anastomoses. The diagnosis of graft rejection and graft-versus-host disease (GVHD) was based on histology of hematoxylin and eosin-stained biopsies from target organs. Recipients of fetal and newborn grafts did not show signs of GVHD, while 12% of the adult group did (P < 0.05). Rejection was less severe in fetal and adult (P > 0.05) than in newborn (P < 0.05) intestinal transplantation. Treatment with 10 mg/kg per day cyclosporine prevented rejection in 70% of fetal and 75% of adult grafts, while all newborn grafts were rejected. Under no immunosuppression, or with low doses of cyclosporine (2 mg/kg per day), all groups showed histologic signs of rejection in almost all cases, the fetal intestine being the least affected. Concerning histocompatibility barriers, grafts were usually less damaged in the weaker transplantation subgroups. Our data indicate that fetal intestine is the least immunogenic of the three grafts studied, suggesting that it will be the most suitable tissue for organ donation.