The functional and morphologic characteristics of free-draining, pancreatic segmental autografts (FDPS) were studied in 8 beagle dogs that had survived longer than 4 yr. After pancreatectomy, animals received FDPS autografts of the left pancreatic limb, representing approximately one-third of the total pancreas with iliac vessel anastamoses. The grafted recipients were given pancreatic enzyme supplements (Viokase). After transplantation (tx), all 8 animals sustained fasting euglycemia with no evidence of microvascular complications. After 4 yr, IVGTT revealed K-values (%/min) that were not significantly different from age-matched controls (2.9 +/- 0.5 versus 3.7 +/- 0.6, P greater than 0.05). Mean fasting serum insulin levels were significantly greater in the tx animals (49 +/- 5 microU/ml versus 12.2 microU/ml, P less than 0.001), although the incremental response to i.v. glucose (0.5 g/kg) was less than in controls (P less than 0.05). Mean fasting plasma C-peptide levels (0.09 +/- 0.01 pmol/ml versus 0.21 +/- 0.5 pmol/ml) and peak C-peptide responses to i.v. glucose were both significantly less than in controls. Sequential pancreatic biopsies up to 2.5 yr post-tx showed atrophy of the exocrine pancreas with coalescence of islets and mild fibrosis that did not progress with time. Immunoperoxidase stains confirmed the presence of insulin, glucagon, and somatostatin within nests of islet cells. Four years after transplantation of FDPS autografts in pancreatectomized dogs, excellent function is retained. The consequences of peripheral hyperinsulinemia remain to be determined.