Many of the substances known to control the secretion of pituitary gonadotropins also modulate the secretion of human chorionic gonadotropin (hCG) by the placenta. In order to study the effect of estrogens and progestins on hCG secretion, term placental explants were cultured in culture media for 144 hours. During the culture period, hCG secretion increased after 48 hours, and a fortyfold increase was observed after 144 hours (p < 0.001). Compared to concentrations of hCG in control cultures, secretion of hCG was markedly suppressed in the presence of progesterone 2.25 × 10-5M (p < 0.001), a concentration similar to that found in term placental tissue (1.7 ± 0.2 μg/gm of tissue). Suppression of hCG by progesterone occurred in a dose-response manner (r = -0.9100, p < 0.01). Estradiol, an important steroid modulator of pituitary gonadotropins, did not significantly suppress the secretion of hCG, except in pharmacologic concentrations (10-4M), and physiologic concentrations of estradiol had no effect on the suppression of hCG by progesterone. These results suggest that the mechanism by which progesterone suppresses the secretion of hCG differs from the manner in which steroids modulate the secretion of pituitary gonadotropins.