This report provides our initial experience on islet isolation and intrahepatic allotransplantation in 20 patients. In Group 1, 10 patients underwent combined liver-islet allotransplantation following upper-abdominal exenteration for cancer. One patient underwent pancreatic islet allograft after near total pancreatectomy for chronic pancreatitis. In Group 2, 3 Type I diabetic patients received a combined liver-islet allograft for cirrhosis and diabetes. In Group 3, 7 Type I diabetic patients received 8 combined cadaveric kidney-islet grafts (one retransplant) for end stage renal disease. The islets were separated by a modification of the automated method for human islet isolation and the preparations were infused into the portal vein. Immunosuppression was with FK-506 (Group 1) plus steroids (Groups 2 and 3). Six patients in Group 1 did not require insulin treatment for 5 to >16 mo. In Groups 2 and 3 none of the patients became insulin-independent, although ongoing C-peptide secretion, decreased insulin requirement and stabilization of diabetes were observed. Our results indicate that islet transplantation is most effective in pancreatectomy induced diabetes. However, rejection is still a major factor limiting the clinical application of islet transplantation in patients with Type I diabetes mellitus. Other factors such as steroid treatment may contribute to deteriorate islet engraftment and/or function.