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Although clinical small-bowel transplantation is still severely hindered by rejection of the graft, prolonged graft survival can be achieved by using cyclosporin A in several experimental models of small-bowel transplantation. In an immunologically quiescent phase after transplantation, the important question arises whether a small-bowel allograft has enough functional capacity to maintain a normal nutritional status. We investigated the functional capacity of orthotopic small-bowel transplants and evaluated the ability of the total small-bowel transplant to absorb orally given cyclosporin in the early postoperative period and the effect of this oral cyclosporin treatment on allograft survival as compared with intramuscular administration. Between 3 and 7 months postoperatively, recipients of syngeneic and allogeneic total small-bowel transplants and syngeneic jejunal segmental grafts had significantly decreased serum triglyceride levels. Total serum protein and albumin concentrations, serum cholesterol values, fecal fat excretion, and percentage of split fatty acids were normal. One year after transplantation the weight in the groups transplanted with a total small-bowel graft was not different from age-matched untreated controls. Animals grafted with a segmental graft, however, showed a significantly impaired growth and had not reached a normal weight 1 year after transplantation. Growth was also significantly impaired after near-total small-bowel resection. These animals had to be killed because of their poor condition. Cyclosporin absorption after small-bowel transplantation equalled that in normal controls. Graft survival after intramuscular treatment, however, was significantly better than after oral treatment.