The mechanism (s) leading to p cell dysfunction in type I diabetes has not been defined. We have investigated whether islet expression of IFNa could be a cause of the lesions that are hallmarks of type I diabetes. Streptozotocin induces the expression of interferon-u by pancreatic islets prior to the diabetes induced by streptozotocin. Increased IFNa, induced by poly I/C or expressed from a transgene will exacerbate the diabetogenie effects of streptozotocin. In another rodent model of type I diabetes (the BB rat), islet expression of IFNa precedes lymphocytic infiltration and diabetes. As in the streptozotocin model, in the BB rats poly I/C will induce islet expression of IFNa and accelerate the onset of diabetes. These results are consistent with the hypothesis that islet expression of IFNa participates in causing type I diabetes.