The extra-ovarian contribution to progesterone levels in the circulation has been measured in ovariectomized ewes in which pregnancy was maintained by treatment with medroxyprogesterone acetate. Since adrenal production of progesterone is low this procedure allows the determination of placental secretion. Placental production of progesterone has been shown to rise initially between 50 and 70 days of gestation, with a second phase of increase between 90 and 120 days of gestation. Both periods of increased secretion of progesterone were reflected in rises in progesterone production by placental explants in organ culture and in the activity of 3 beta-hydroxysteroid dehydrogenase in the tissue. The activity of 3 beta-hydroxysteroid dehydrogenase exceeded the rate of progesterone production by approximately 30-fold, and it appears unlikely, therefore, that this enzyme is rate-limiting in the synthesis of progesterone. Surgical reduction of the number of cotyledons led to compensation by an increase in weight of individual cotyledons with no significant increase in specific 3 beta-hydroxysteroid dehydrogenase activity or rate of production of progesterone in organ culture. It was concluded that the rise in placental production of progesterone in the middle period of gestation is unlikely to result either from an increase in 3 beta-hydroxysteroid dehydrogenase activity or from exposure to factors stimulating placental growth.