The administration of the Islet-Activating Protein (IAP) of pertussis toxin results in an increased insulin response to oral glucose in a dose- dependent manner. This response can be detected for up to 12 days after a single injection. In addition, IAP increases the number of peripheral blood leucocytes and lymphocytes. Inbred strains of rats differ in the magnitude of the leucocyte but not the insulin responses to IAP. Multiple injections of 1,000 ng of IAP to diabetes-prone BB rats at 50, 64 and 78 days of age caused an increased release in response to glucose challenge and a slight increase in peripheral blood leucocytes when compared to animals receiving saline injections. The prevalence of insulin-dependent diabetes in BB rats was increased in the IAP group as compared to controls. Histolgic examination of the pancreas at the time of detection of diabetes revealed a widespread intense insulitis. We speculate that the increased expression of disease observed in the BB rats receiving IAP may be secondary to the chronic increase in insulin release and/or to an effect on the cells of the immune system.