OBJECTIVE The purpose of this study was to examine the effect of chronic fetal placental embolization on fetal plasma prostaglandin E2 concentrations. METHODS Fourteen pregnant sheep were studied (seven embolized and seven controls) for 10 days between 0.84 and 0.91 of gestation. Daily injections of nonradioactive microspheres were made to decrease fetal arterial oxygen content by 30% to 35% of preembolization values. RESULTS In response to repeated embolization, fetal plasma prostaglandin E2 concentrations increased significantly on day 1, declined to near control levels on days 2 to 6, but were significantly elevated again after day 7. Maternal prostaglandin E2 levels remained unchanged throughout the study. Fetal plasma prostaglandin E2 levels increased significantly with decreasing fetal oxygenation when fetal arterial oxygen content was < 2.0 mmol/L. CONCLUSIONS We conclude that there is increased production of prostaglandin E2 by the placenta during progressive fetal hypoxemia induced by fetal placental embolization. We speculate that the progressive increase in prostaglandin E2 may be an important hormonal adaptive mechanism to maintain fetal homeostasis during the development of placental insufficiency.