There is much evidence indicating that in man and animals the hypophysis and adrenal cortex begin to function during the prenatal period. It is still not clear, however, whether a feedback relationship typical of the adult organism is established between these glands. Accordingly, we have investigated the effect of corticosteroids on the adrenocorticotrophic function of the hypophysis of the rat fetus. Changes in the concentration of corticosteroids in the blood were produced in gravid rats by administration of hydrocortisone, surgical trauma or by adrenalectomy. All experimental manipulations were started at 19 days of pregnancy, and autopsies were performed at 22 days. After stress (sham adrenalectomy) inflicted on a gravid rat, the concentration of ACTH in the fetal hypophysis was reduced from 1.9 mU per hypophysis to 0.68 mU per hypophysis. After 3 days of daily administration of 4.0 mg of hydrocortisone no ACTH could be found in fetal hypophysis. Hydrocortisone simultaneously caused a loss of weight of the adrenals in mothers and fetus (p < 0.001) and an increase of concentration of ascorbic acid in the glands (p < 0.001). Following adrenalectomy of the mother the concentration of ACTH in the fetal hypophysis is reduced to 0.62 mU per hypophysis and the weight of the adrenals is increased from the control value 48.6 ± 1.4 mg/100 gm of body weight to 73.1 ± 1.3 mg/100 gm of body weight (p < 0.001). The low level of ACTH in the pituitary gland in the presence of increased weight of the adrenals may indicate an intensive secretion of ACTH from the pituitary. The results of these experiments demonstrate that the high concentration of corticosteroids in the blood inhibits adrenocorticotrophic function of fetal pituitary gland whereas the low concentration stimulates it. Thus, in the rat during embryonal development a feedback relationship typical of adult organisms is established between the pituitary gland and the adrenals. © 1968.