In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same JcI:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts from NOD mice into ILI-nu/ nu mice and those from ILI mice into NOD-nu/nu mice failed to allow the development of insulitis, implying that ILI mice possess neither precursor T cells nor the thymic environment responsible for the development of insulitis. In addition, splenocytes from ILI mice appeared to contain regulatory cells which suppress the development of diabetes but not that of insulitis in NOD mice. The use of these nude mice should provide more information on the products of insulitis-susceptibility genes of NOD mice.