The normal development of the fetus requires an adequate transfer of nutrients and oxygen from the maternal to fetal circulation and a movement of fetal carbon dioxide and other waste products in the opposite direction. The major determinants of placental transfer are placental blood flow and placental permeability. However, in numerous physiological and pathophysiological conditions placental blood flow may be significantly compromised and this reduction in placental blood flow may lead to a severe alteration in the fetal environment. When the fetus is chronically exposed to this hemodynamic alteration, there is an increased incidence of premature labor, intra-uterine growth retardation and pre-eclampsia. These complications of pregnancy are also directly associated with an increased incidence of brain damaged and metally retarded offspring. The present proposal outlines an extensive study into the effects of reduced uterine (placental) blood flow on the fetal lamb and the pregnant ewe. The reduction in blood flow will be carefully controlled and continuously monitored. During the reduction in uterine blood flow, maternal and fetal cardiovascular, respiratory and basic biochemical parameters will be monitored. The role of the renin-angiotensin system and vasodilator prostaglandins in compensating for the reduction in uterine blood flow will be investigated. This integrated study of the effects of reduced uterine blood flow in the maternal and fetal sheep should provide a better understanding of the mechanisms by which the pregnant ewe and her fetus compensate for uterine vascular insufficiency.