Immune rejection following transplantation of non-encapsulated pancreatic islets has remained a major obstacle to successful treatment of type I diabetes, despite the use of high-dose immunosuppressive drugs with their potentially severe side-effects. Encapsulation circumvents the need for immunosuppression because the transplanted living cells are surrounded by a semipermeable membrane which protects them from the host's immune system. Unfortunately, clinical applications of early encapsulation devices were hampered by their mechanical fragility, their limited surface area, and their need for a major surgical procedure. Although new microencapsulation technologies dispense with many of these issues, not all semipermeable membranes can form a biocompatible and mechanically stable immunoprotective system which allows sufficient oxygenation of the cells as well as adequate insulin diffusion. Alginate-polylysine spherical-bead microcapsules (with improved biocompatibility, mechanical strength, and chemical stability) can now provide a large surface area, enhanced nutrition and oxygen supply, precisely tailored porosity (to discriminate nutrients from immunoglobulins), maximum protection from membrane failure, and direct injectability into the peritoneal cavity. Our objective was to test the therapeutic effectiveness of alginate-polylysine microcapsules for the transplantation of human-insulin-producing cells into a human diabetic patient, a 38-year-old white male with insulin-dependent diabetes for 30 years. Encapsulated islets (10,000 islets/kg) were injected directly into the peritoneal cavity through a 2 cm midline incision. Insulin secretion from the transplanted cells was detected within 24 h after injection, and has continued for more than 58 months. The patient reported significant improvement in the quality of his life including a decrease in his lower extremity peripheral neuropathy symptoms, an increased energy level, an ability to walk further, a general feeling of improved health, and no adverse effects.