The diagnosis of pancreas allograft rejection is usually made on the basis of blood glucose concentration, a late indicator of rejection. We performed segmental pancreas transplants in totally pancreatectomized dogs with the exocrine secretions drained into the bladder (ductocystostomy). We directly measured exocrine pancreatic secretions (urinary amylase), in an attempt to find a sensitive indicator for early rejection. Five groups were studied: (I) autografts; (II) autografts immunosuppressed with cyclosporine (CsA), azathioprine and prednisone; (III) allografts without immunosuppression; (IV) allografts immunosuppressed with CsA alone; (V) allografts immunosuppressed with CsA, azathioprine, and prednisone. The control groups (I, II) maintained high urine amylase concentrations indefinitely (mean +/- SE of 125,544 +/- 36,931 u/liter). Rejection, as diagnosed by rise of serum glucose to greater than 150 mg/dl, occurred at a mean (+/- SE) of 9.0 +/- 0.2 days in nonimmunosuppressed recipients of Group III, at 9.3 +/- 0.7 days in cyclosporine-treated dogs of Group IV, and at 28.0 +/- 8.3 days after transplantation in dogs immunosuppressed with triple therapy of Group V. In all allograft recipients, urine amylase declined precipitously (less than 1000 u/liter) before the onset of hyperglycemia, by 1.3 +/- 0.2 days in Group III, 3.3 +/- 1.0 days in Group IV, and 9.4 +/- 2.8 days in Group V. In a further experiment, nine dogs with pancreas allografts received cyclosporine for prophylactic immunosuppression; further antirejection therapy with azathioprine and antilymphocyte globulin was given for 5 days beginning the first day that rejection was diagnosed. In five dogs (Group A) rejection was diagnosed when serum glucose rose to greater than 150 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)