Glucose metabolism and insulin secretion after pancreas transplantation may be affected by the technique used for ductal drainage. We evaluated peripheral glucose and insulin levels after oral (oral glucose tolerance test [OGTT]) and sustained stable hyperglycemic challenge (clamp) in dogs who had undergone pancreas autotransplantation with intraperitoneal drainage (PAT) or with urinary bladder to pancreatic duct anastomosis (PAT/B). Both groups had basal glucose values comparable to normal controls; PAT/B animals had fasting hyperinsulinemia. Pancreas autotransplantation animals had an increased integrated glucose response to OGTT and blunted insulin response to hyperglycemic clamp. Urinary bladder to pancreatic duct anastomosis animals had a significantly decreased integrated glucose response to OGTT compared to PAT and an exaggerated insulin response to hyperglycemic challenge, which approximated normal control values by the last 30-minute period of the clamp. Interestingly M values, which approximate glucose metabolized during the hyperglycemic challenge, were depressed in both surgical groups. It is concluded that the technique of bladder drain-age allows a 'normalization' of peripheral levels of insulin that is associated with amelioration of an altered glucose response after oral challenge. However the clamp studies show that, despite the improvement in insulin response, an insensitivity may exist to a wide range of endogenous levels after pancreas transplantation.