Islet transplantation is a new therapeutic approach to type 1 diabetes mellitus. However, in several patients insulin levels are not restored and the glycemic control is inadequate. To clarify the cause of graft failure, the authors investigated with light and electron microscopy some human islet grafts before and after transplantation under the kidney capsule of streptozotocin-induced diabetic nude mice. In isolated islets, both pre- and post-transplantation, the endocrine component was scarcely represented, the beta/alpha cell ratio was reduced, and beta cells showed degenerative aspects such as apoptosis, immature secretory granules, and amylin fibrils deposition. The authors conclude that islet graft failure may be due to an insufficient beta cell mass related to their distress probably caused by anoxia and/or overstimulation.