To determine the role of placental progesterone in the onset of labor, tissue progesterone concentrations and in vitro conversion of tritiated pregnenolone to progesterone were examined in the placentas, chorion, and amnion of 12 term pregnancies delivered by cesarean section with or without labor and vaginal delivery. In all instances, the placenta had significantly higher progesterone concentrations than the chorion or amnion. Progesterone concentrations in the chorion were significantly lower after the onset of labor than before. The placenta and chorion but not the amnion converted pregnenolone to progesterone; the placenta had a significantly greater conversion rate than the chorion in all instances. Placental conversion of pregnenolone to progesterone increased significantly after labor to reach a maximum with vaginal delivery. Chorionic conversion of pregnenolone to progesterone was significantly increased after vaginal delivery but was similar after cesarean section with or without labor. The reduced tissue progesterone in the chorion, together with enhanced placental and chorionic production of progesterone from its precursor, pregnenolone, suggest that rapid metabolism and increased binding of progesterone locally in the placenta and membranes may lead to the local withdrawal or decline of progesterone and onset of labor.