Cyclophosphamide promoted the onset of overt diabetes in non-obese diabetes-prone mice of both sexes. Two injections of this agent at 2 weeks apart were necessary to obtain a constant high incidence, although even a single injection was effective in some animals. Clinical symptoms of the cyclophosphamide-induced diabetes were similar to those of the naturally occurring type. The same schedule of cyclophosphamide treatment failed to induce diabetes in non-diabetic mouse strains, such as DS/Shi,Jcl:ICR or in non-obese non-diabetes-prone mice, which suggests that the promotion of diabetes by cyclophosphamide in non-obese diabetes-prone mice is not due to the simple pharmacological action of this agent but to some immunopharmacological action.