Objective: The purpose of this study was to examine cellular fibronectin levels throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy. Study Design: Blood samples were collected at 4-week intervals from 378 healthy, nulliparous women who were recruited before 16 weeks of gestation. Preeclampsia developed in 26 patients; 52 normotensive control subjects were matched from the same cohort. Plasma samples were assayed for ED-B fibronectin by enzyme-linked immunosorbent assay. Trends were compared between groups. Predictive values were determined with the use of second trimester assessments. Results: In both groups, fibronectin levels rose as pregnancy advanced, but in women with preeclampsia, this increase was significantly higher (94.5% vs 31.8%; P = .006). Throughout pregnancy, patients with preeclampsia exhibited significantly higher fibronectin levels than did control subjects. As early as 9 to 12 weeks of gestation, a difference was established (preeclampsia, 3.72 ± 0.21; control, 2.94 ± 0.22 μg/mL [mean ± SEM]; P = .008). The best cutoff point and time interval to calculate predictive values were 3.8 μg/mL and 22 to 26 weeks of gestation, respectively. Sensitivity, specificity, and positive and negative predictive values were 73%, 87%, 29%, and 98%, respectively; the odds ratio was 16.1 (95% CI, 8.6-30.2). Conclusion: In women in whom clinical preeclampsia developed, endothelial damage seemed to be present since early gestation. Cellular fibronectin levels of ≥3.8 μg/mL within 22 to 26 weeks of gestation may help in the early detection of preeclampsia in healthy nulliparous women. (Am J Obstet Gynecol 2002;187:595-601.)