In the University of Pittsburgh experience, the most successful setting for human islet allografts is in patients undergoing upper abdominal exenteration with total pancreatectomy and liver transplantation for the indication of malignancy (cluster). In this group of patients 6/11 were insulin-independent for long periods. We report herein the metabolic course or the longest survivor (>3 years). This patient has been free of exogenous insulin since the third postoperative month and has sustained her body weight without total parenteral nutrition since the 4th postoperative month. The patient has some postprandial hyperglycemia but average capillary glucoses are near-normal to normal as are glycosylated hemoglobin values. The clearance of glucose during the administration of an intravenous glucose load has been well preserved and is currently normal. C-peptide stimulates significantly in response to intravenously injected glucose. The absolute levels of stimulation during the test have declined possibly related to improvements in renal function, decreased immunosuppression or the natural history of cells transplanted into the portal site. The kinetics of the C-peptide response to intravenously injected glucose shows a persistent abnormality of first-phase insulin release and a prolonged second phase release. Basal glucagon levels are low but stimulate to a mixed meal. This patient's results demonstrate long-term function of islet cells from a single donor transplanted into the portal vein using FK506 as an immunosup-pressant agent.