Preeclampsia is a systemic disease characterized by diffuse endothelial dysfunction, increased peripheral vascular resistance, coagulation abnormalities, antioxidant deficiency, persistent elevations of maternal leukocyte-derived cytokines, and hyperlipidemia. Fish oil, rich in omega-3 polyunsaturated fatty acids, is known to reduce fasting and postprandial triglycerides and to decrease platelet and leukocyte reactivity; it may also decrease blood pressure. Additionally, omega-3 fatty acids may beneficially influence vessel wall characteristics and blood rheology. In light of the potential beneficial effects of dietary omega-3 fatty acids, we conducted a cross-sectional case-control study to examine the hypothesized exposure-effect relation between maternal dietary intake of marine omega-3 fatty acids and risk of preeclampsia. We measured polyunsaturated fatty acids in erythrocytes obtained from 22 preeclamptic women and 40 normotensive women; we measured polyunsaturated fatty acids as the percentage of total fatty acids from gas chromatography. We employed logistic regression procedures to estimate odds ratios (ORs) and 95% confidence intervals (CIs). After adjusting for confounders, women with the lowest levels of omega-3 fatty acids were 7.6 times more likely to have had their pregnancies complicated by preeclampsia as compared with those women with the highest levels of omega-3 fatty acids (95% CI = 1.4-40.6). A 15% increase in the ratio of omega-3 to omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia (OR = 0.54; 95% CI = 0.41-0.72). Low erythrocyte levels of omega-3 fatty acids and high levels of some omega-6 fatty acids, particularly arachidonic acid, appear to be associated with an increased risk of preeclampsia.