The presence of all components of the renin-angiotensin system within the human placenta appears to be well established, but their function and regulation remain obscure. In order to approach this question, placental tissue explants (50 mg) from early human placenta (9-12 weeks of gestation) were cultured in Medium 199. Prorenin was measured by direct immunoradiometric assay in the daily replaced culture medium. In a further series of experiments, progesterone, a progesterone antagonist (ZK 98,299) or estradiol was added to the medium at final concentrations of 10(-4)-10(-8) mol/l. Prorenin was detectable in the culture medium of early human placental explants, and prorenin values were decreased by progesterone in a dose-dependent manner. Progesterone antagonist and estradiol could also inhibit prorenin secretion, but the inhibition was less prominent. When progesterone and progesterone antagonist were co-administered at equimolar concentration, a decrease in prorenin secretion occurred, but it could not reach the inhibitory effect of progesterone given alone. It is concluded that prorenin activity is present in the early human placenta, and prorenin secretion may be influenced by progesterone and estradiol. Regulation of prorenin secretion by steroid hormones is partly similar to that of human chorionic gonadotropin, but its physiological significance awaits further exploration.