Background. Pancreas transplantation has been shown to fully restore glucagon response and partially restore epinephrine response to hypoglycemia during the first few years after transplantation in patients with type 1 diabetes. However, prior studies have not examined hypoglycemic counterregulation in any pancreas transplant recipient of more than 6 years' duration. Methods. To determine whether restoration of hypoglycemic counterregulation is maintained over a prolonged period after transplantation, we studied counterregulatory responses and symptom recognition in two groups of pancreas transplant recipients using a stepped hypoglycemic, hyperinsulinemic clamp. Group 1 consisted of 11 successful transplant recipients of 11 to 19 years' duration (mean±SE, 13.9±0.7 years). Group 2A consisted of seven successful pancreas transplant recipients of 5 to 11 years' duration (mean±SE, 8.7±0.9 years) who had been studied approximately 5 years earlier using the same stepped, hypoglycemic clamp technique. Results. Both groups had significant rises in plasma glucagon during the hypoglycemic clamp similar to that seen in short-term recipients and normal controls. Both groups also had significant increases in plasma epinephrine responses similar to that seen in short-term transplant recipients but less than that of normal control subjects. The mean symptom scores of group 1 were significantly less than those of the control group at glucose levels of 60 and 50 mg/dL but not at 40 mg/dL. The mean symptom scores of group 2A were not significantly different than that of control subjects. Conclusion. These results indicate that the restoration of hypoglycemic counterregulation by pancreas transplantation remains stable in successful pancreas transplant recipients for up to 19 years after transplantation.