Vascular endothelial growth factor receptor-1 (VEGFR-1) is essential for the normal development and function of the placenta. Defective placental vasculogenesis and trophoblast function may lead to pre-eclampsia, a pregnancy-specific syndrome of hypertension and proteinuria. In order to study the association of VEGFR-1 with the development of pre-eclampsia, a cross-sectional study was carried out to evaluate the concentration of soluble VEGFR-1 (sVEGFR-1) in 360 serum samples and to analyze the expression of membranous VEGFR-1 in 40 placental samples of normal and pre-eclamptic pregnant women. Serum and placental samples at different gestational ages were collected from the Department of Obstetrics and Gynaecology, VMMC and Safdarjang Hospital, New Delhi. The serum levels of sVEGFR-1 and the expression of membranous VEGFR-1 were estimated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The serum levels of sVEGFR-1 were seen to be positively increased (p=0.0001) in patients with pre-eclampsia at different gestational intervals as compared to the healthy pregnant women they were matched with. However, receiver operating characteristic (ROC) curve analysis showed a higher sensitivity (89.17%) and specificity (90.0%) in early onset (< or =34 weeks) in contrast with the late-onset (>34 weeks) pre-eclamptic group. Also, significant up-regulation of membranous VEGFR-1 immunoreactivity was observed in all placental cells (syncytiotrophoblast, cytotrophoblast, endothelial cells and Hofbauer cells) of pre-eclamptic groups in both < or =34 weeks (p=0.0001) and >34 weeks (p=0.0001) as compared to the normal group. Elevated sVEGFR-1 serum levels and up-regulated membranous VEGFR-1 expression in placenta denote abnormality in VEGF-mediated function in all placental cells, and thus may contribute to etiopathogenesis of pre-eclampsia. Nevertheless, this study also shows the possible diagnostic utility of sVEGFR-1 as a sensitive and specific biomarker for the early onset (< or =34 weeks) of pre-eclampsia.