Nonobese diabetic (NOD) mice develop autoimmune diabetes with features similar to those observed in the human disease. The concurrence of allorecognition and recurrence of autoimmunity might explain why most of the treatments successful in preventing islet allograft destruction in other nonautoimmune combinations often fail in NOD recipients. To assess the value of the NOD mouse model for the evaluation of treatments relevant to clinical islet transplantation, the authors have tested the effect of a protocol closely resembling the one successfully used in the Edmonton clinical trial on the survival of islet allografts in NOD mice.