OBJECTIVE To evaluate the long-term effect on blood glucose levels of successful transplantation of part or all of an intact human pancreas in patients with insulin-dependent diabetes mellitus (IDDM). METHODS Cohort study. METHODS Referral medical center. METHODS Thirty-seven patients with adequate data, representative of a group of 62 patients with functioning grafts (that is, insulin-independent) at 2 years after transplantation. The 62 patients came from a total of 178 patients in the University of Minnesota series as of July 1987, for a 2-year success rate of 35% (95% Cl, 27.8% to 41.8%). These patients were compared to two diabetic control groups (18 patients with IDDM under standard insulin treatment in a university diabetes clinic and 11 patients with IDDM whose pancreas grafts had failed) and to two nondiabetic groups (14 nondiabetic patients who received immunosuppressive drugs after kidney transplantation and 196 healthy control subjects). METHODS Glycosylated hemoglobin was measured by the high-pressure liquid chromatography method, as total A1 (Hb A1) and the A1C subfraction (Hb A1C); results were expressed as a percentage of total hemoglobin. RESULTS Before pancreas transplantation, the 37 patients in the study group had a mean Hb A1 of 10.8%, consistent with moderate to marked hyperglycemia and not statistically different from the levels in the diabetic control groups. All 37 patients had values above the therapeutic target range of 5.4% to 7.4%. However, at 1 and 2 years after transplantation, the mean Hb A1 value had fallen sharply to 6.7% and 6.5%, respectively, well within target range (Cl of the difference, 3.4% to 4.8%; P less than 0.001). These levels did not differ from the mean Hb A1 in the nondiabetic kidney transplant recipients but were slightly above the 6.2% value for the 196 healthy controls (Cl of the difference at 1 year, 0.2% to 0.8%). Serial values were available on 6 subjects for 5 years; these values were all well within target range. As expected, Hb A1C values were parallel to those of Hb A1. CONCLUSIONS Pancreas transplantation, in our successful cases, lowered glycosylated hemoglobin to normal or near-normal levels that were sustained for as long as 5 years. These results compare favorably with those in our patients on standard treatment, and also with those in similar patients on intensive control reported by others. Further effort to improve transplant methods appears to be warranted.