Female PVG/c strain rats are more susceptible to the induction of autoimmune thyroiditis initiated by thymectomy and irradiation (Tx-X) than similarly treated males. Pre-pubertal ovariectomy was found to further augment this susceptibility. The administration of oestrogen or progesterone to groups of 4 week old ovariectomized Tx-X animals over a period of 15 weeks significantly altered the course of the events leading to the induction of this condition. Thus oestrogen administered repeatedly at dose levels of 1 microgram and 10 micrograms/100 g body weight resulted in partial suppression of thyroiditis with a corresponding change in the incidence of antibodies to thyroglobulin. Similarly, oestrogen administered by a single implantation had a suppressive effect on the development of autoimmunity in ovariectomized Tx-X females. Oestrogen given by either of these procedures also reduced the incidence of both thyroiditis and autoantibody induction in orchidectomized male Tx-X rats. In contrast to the inhibitory effects of oestrogen, the repeated administration of progesterone at a dose of 250 ng and 1,500 micrograms/100 g body weight appeared to augment the levels of autoimmunity. It is concluded that the differential susceptibility to the induction of autoimmunity by thymectomy and irradiation is the direct consequence of sex hormonal influences. Furthermore, the higher incidence of the disease in the female would appear to be determined by the balance between the activity of oestrogen and progesterone which would further appear to have antagonistic influences in this particular situation.