Despite improving results, the management of exocrine complications after pancreas transplantation remains problematic. During a 30-month period, we performed 65 pancreas transplants with bladder drainage. A total of 23 patients (35%) were managed with a long-acting somatostatin analogue (Sandostatin) for persistent hyperamylasemia or allograft pancreatitis. Sandostatin was begun at a mean of 29 days after transplant with a mean duration of therapy of 13 days. Sandostatin therapy was associated with significant reductions in the serum, urine, and peritoneal fluid amylase levels (p < 0.05). Sandostatin also caused a decrease in cyclosporine levels during oral cyclosporine use. In patients receiving Sandostatin, pancreas allograft survival was 83%. We conclude that pancreatitis remains a major cause of morbidity after pancreas transplantation. The selective use of Sandostatin can result in excellent graft salvage with low morbidity. Sandostatin appears to be safe and effective in reducing the exocrine output of the denervated pancreas allograft but also reduces cyclosporine levels.