Objective: To study the plasma levels of homocysteine in preeclampsia and relate them to insulin sensitivity. Methods: In association with a 3-hour intravenous glucose-tolerance test (glucose 0.3 g/kg at 0 and 0.03 IU insulin 20 minutes later), we measured plasma levels of homocysteine, vitamin B-12, and folic acid in 22 women with preeclampsia and 16 controls between 29 and 39 weeks' gestation. In 14 women with preeclampsia and 11 controls, plasma samples also were collected 3 months after delivery. Results: Levels of homocysteine in women with preeclampsia (6.7 +/- 0.4 mu mol/L, mean +/- standard error) were higher (P <.001) than those in controls (3.8 +/- 0.2 mu mol/L) and related significantly to the level of proteinuria (r =.49, P =.02). Vitamin B-12 concentrations were lower in women with preeclampsia (166.0 +/- 10.4 compared with 212.4 +/- 16.4 pmol/L, P =.02), whereas levels of folic acid showed no difference between the groups. After delivery, levels of homocysteine increased to 9.1 +/- 0.6 and 8.2 +/- 0.6 mu mol/L in women with preeclampsia and controls, vitamin B-12 increased to 298.8 +/- 28.6 compared with 334.9 +/- 24.0 pmol/l, and folic acid decreased to 10.6 +/- 2.0 compared with 7.9 +/- 0.8 nmol/L, with no difference emerging between the groups. In women with preeclampsia but not in controls, plasma homocysteine was negatively related to insulin sensitivity (r = -.51, P =.02). The mean 2.9-fold increase in glucose or 52.5-fold increase in insulin during the insulin-sensitivity test failed to affect homocysteine levels. Conclusion: Women with preeclampsia have high plasma homocysteine levels that are inversely related to insulin sensitivity. (Obstet Gynecol 1999;93:489-93. (C) 1999 by The American College of Obstetricians and Gynecologists.).