Objective: To assess whether alterations in the serum levels of placental growth factor, activin A and fibronectin could be detected in patients before they become preeclamptic. And to evaluate and compare the clinical utility of these markers and uterine artery Doppler velocimetry in predicting preeclampsia. Methods: One hundred and twenty-two normotensive women were prospectively included in the study. Peripheral venous blood samples were obtained and Doppler examination of the uterine arteries was performed between 21 and 26 weeks' gestation. Serum levels of placental growth factor, activin A and fibronectin were measured by enzyme-linked immunoassay and radial immundiffusion technic. Results: Mid-trimester maternal serum activin A and fibronectin levels and average S/D ratios were significantly higher whereas placental growth factor levels were significantly Lower in women who subsequently developed preeclampsia than remained normotensive (p < 0.001). The best cut-off values for predicting preeclampsia of placental. growth factor, activin A and fibronectin based on. ROC curve analysis were 90 pg/ml, 14 ng/ml and 370 mg/l respectively. The areas under the curve equal to 0.993, 0.972, 0.872 and 0.813 for placental growth factor, activin A, fibronectin and uterine artery Doppler respectively were determined for the prediction of preeclampsia. Conclusion: Placental growth factor, activin A, fibronectin and uterine artery Doppler are all potentially useful as predictors of preeclampsia. Maternal serum midtrimester PGF has the highest predictive value and activin A with a compatible accuracy for early identification of preeclampsia. (c) 2005 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.