To examine the influence of sex hormones on the appearance of overt diabetes in NOD mice, oophorectomy and orchiectomy were performed. Castrated males showed a high incidence of diabetes. The time course of onset was similar to that of the intact females. On the other hand, castrated females showed a intact-male pattern of onset with a low incidence. Clinical determinations demonstrated a close similarity between spontaneous and castration-induced diabetes. These data suggest that sex hormones modulate the expression of overt diabetes in NOD mouse, i. e. androgens have at least a suppressive effect.