Prolonged administration of glycyrrhetinic acid was studied in immature female rats, castrated male donor parabionts, and mature cyclic rats. Glycyrrhetinic acid treatment for 7 days interfered with the uterotrophic response of immature rats to estradiol benzoate but had no effect on the pituitary-ACTH content. It did not alter gonadotropin release or estradiol-induced gonadotropin inhibition in male castrated donors. One month of treatment did not alter the estrus cycles. It is apparent that the antiestrogenic effect of glycyrrhetinic acid is limited to exogenous estrogen and its effect on the female accessory reproductive tract.