Type I diabetes has resisted direct genetic analysis in humans but two excellent models of disease in rodents provide a more readily manipulated alternative for study. These rodent models are being used successfully to localize the genes that are involved in disease pathogenesis in preparation for positional cloning. In addition, mice carrying transgenes and null mutations related to T cell function have been used to demonstrate potential mechanisms for both MHC-dependence and specific effector functions, such as cytokine release and cytotoxicity.