Our laboratory studies the role of angiogenic factors in the pathogenesis of preeclampsia, one of the most common medical complications of pregnancy. We have demonstrated that placental overproduction of a soluble vascular endothelial growth factor receptor (sFlt1 or sVEGFR1), an anti-angiogenic protein, mediates the hypertension and proteinuria of preeclampsia. Circulating sFlt1 also antedates the appearance of overt disease and thus measuring this protein in the blood during pregnancy can serve as a screening test. We have continued to explore the complex biology of preeclampsia, uncovering an additional synergistic protein, soluble endoglin (sEng) that is overproduced in the placenta and also a likely mediator of disease manifestations. We are currently studying the etiology of the increased sFlt1 and sEng in preeclamptic patients and exploring whether these markers can be used for the diagnosis and prediction of preeclampsia. Methods aimed at interfering sFlt1 and sEng may also serve as a novel therapeutic strategy in patients with severe preeclampsia.