Protective effect of pertussis vaccine (PV) against the development of insulin-dependent diabetes (IDD) induced by streptozotocin (STZ) in young CD-I male mice were studied. When PV at a dose of 1.2 X 1010microorganism was administered on —10, 0, or +4 d relative to a single injection of STZ (60 mg/kg body wt) on d 0, it completely aborted the development of IDD after 140 d. When PV was given on +30 d after STZ injection and followed by PV booster injections, 66% of mice reverted to normoglycemic state. Intact islet cells in the pancreas were confirmed by histologic findings and normal plasma insulin values. The effect of PV was compared with that of boiled PV in another model of IDD induced by multiple injections of STZ (40 mg/kg for five doses). In this model, 60% of mice either remained or reverted to normoglycemic state with PV and booster injections whereas boiled PV protected 40% of mice from developing IDD. The protective effect appeared to reside in the biologic property of both pertussigen and endotoxin of Bordetella pertussis.