Vascular endothelial growth factor (VEGF) is a potent angiogenic agent, inducing both growth and chemotaxis in endothelial cells and new blood vessel formation. VEGF is expressed throughout normal gestation, in syncytiotrophoblasts and invading extravillous trophoblasts. It is also found in maternal and fetal macrophages. VEGF might be important to maternal and fetal parts of the placenta for development of the vascular system. Since trophoblasts express VEGF receptors, they are also potential targets for VEGF activity. In preeclamptic placentas, the reported inadequate vascularization and growth of trophoblastic villi might be linked to lower VEGF production in these patients. Previous data on VEGF in blood samples from preeclamptics have not been consistent, we believe, because many investigators used a sandwich ELISA technique not suitable for biological fluids. In this study we use an improved competitive enzyme immunoassay (CEIA) designed to measure both the free and bound forms of VEGF in the plasma (total VEGF). VEGF levels were assessed by a Cytokit Red “Competitive” assay obtained from CYTImmune Sciences, Inc., College Park, MD. Blood was collected into sodium citrate from term preeclamptic (n=12), control pregnant subjects (n=12) and non-pregnant volunteers (n=10). Total VEGF plasma levels (ng/ml) in the preeclamptic patients (23.1±3.7se) were significantly lower than in controls (65.8±9.4se; p=0.0003). The plasma VEGF of non-pregnant women(26.2±5.3se) did not differ from the preeclamptic patients. These results combined with a report of decreased VEGF mRNA in placentas of preeclamptic women (1996; Br J Obstet Gynaecol 103:1191-1196) suggest that the plasma VEGF is most likely placentally derived. In summary, down regulation of placental VEGF mRNA might result in deficient vascularization, growth and differentiation of the trophoblastic villi in preeclamptic placentas and explain the reduced plasma VEGF concentration we observed. The molecular mechanism(s) responsible for the reduced VEGF in preeclampsia and its implication for placental-fetal development remain to be investigated.