The formation of the corpus luteum, its maintenance throughout pregnancy and the secretory activity of this transient endocrine gland receive special emphasis because of its role in the secretion of progesterone. An inadequate luteal phase has been associated with an increased incidence of congenital abnormalities. Anything which interferes with the hormonal environment may lead to fetal death or abnormal embryogenesis. Retinoic acid was administered to mice early in pregnancy to induce neural tube defects. Plasma concentrations were determined by high pressure liquid chromatography. Distribution of the retinoic acid was determined by wholebody autoradiography. The hormonal profile during pregnancy was determined in control and retinoic acid treated dams by specific radioimmunoassay for progesterone and 20 alpha dihydroprogesterone. There was no significant effect of retinoic acid on the hormonal profile of treated dams. This suggests that the teratogenic effects of retinoic acid are not due to a change in the hormonal environment. Progesterone and 20 alpha dihydroprogesterone concentrations were significantly increased on days 10 and 10.5 of pregnancy in both treated and control dams. This is the point when pseudopregnancy would end and pregnancy maintenance comes under the control of luteinizing hormone. The increase in 20 alpha dihydroprogesterone concentration at this point in pregnancy was similar to that observed after the administration of prostaglandin F_2alpha (PGF_2alpha). It seems likely that PGF_2alpha and luteinizing hormone act antagonistically during midpregnancy. Concomitant treatment revealed an interaction resulting in an increased progesterone secretion and the conversion of progesterone to 20 alpha dihydroprogesterone. Hence, PGF_2alpha may be released at the point in pregnancy when luteinizing hormone takes over as the major luteotrophin. Luteinizing hormone thus maintains pregnancy in the mouse in the face of an endogenous PGF_2alpha release.