The control of secretion of the placental hormones human chorionic gonadotrophin (hCG) and human placental lactogen (hPL), and the trophoblastic protein pregnancy-specific beta-glycoprotein (SP1), is not well understood. During pregnancy, the hCG concentrations peak in the first trimester then decrease, while hPL and SP1 increase steadily throughout gestation. In order to determine whether the discordance between hCG secretion and that of hPL and SP1 observed in vivo also occur in vitro, we cultured placental explants with and without dibutyryl cyclic AMP (dbcAMP) and theophylline. Between 5 and 12 explants were used for each treatment in each experiment. The concentration of the proteins secreted into the media each day was measured by specific radioimmunoassays. The quantities of hPL and SP1 secreted per day declined in a parallel fashion after 24 hours under both basal and dbcAMP-stimulated conditions. The hCG output progressively decreased in the unstimulated cultures until 48 hours, at which time an increase in hCG secretion was observed. The dbcAMP-stimulated placentae significantly increased their hCG output at both 48 and 72 hours. These data show that hCG secretion is regulated differently from that of hPL and SP1. The results do not negate the possibility that term placental tissue may contain an inhibitor of hCG release that is removed by experimental manipulation in vitro.