The role of individual fatty acids in blood pressure regulation is unclear. We studied the cross-sectional relationship of blood pressure, total plasma phospholipid fatty acid concentrations, and proportions of individual fatty acids among participants in a population study. Blood pressure was measured automatically, and plasma phospholipid fatty acids were determined by gas-liquid chromatography in 4033 healthy men 40 to 42 years old. Significant positive linear associations existed between total fatty acids and saturated fatty acids and blood pressure, whereas polyunsaturated linoleic acid was inversely associated with blood pressure. In multiple regression analyses, a 2-SD increase in total fatty acids was associated with an increase of 6.0 (95% CI, 5.1 to 6.8) mm Hg systolic blood pressure. A 2-SD increase in saturated palmitic acid was associated with 1.4 (95% CI, 0.5 to 2.3) mm Hg increase in systolic blood pressure. In contrast, a 2-SD increase in polyunsaturated linoleic acid was associated with a 1.9 (95% CI, 1.0 to 2.8) mm Hg decrease in systolic blood pressure. We conclude that plasma levels of total fatty acids, saturated fatty acids, and polyunsaturated linoleic acid are independently associated with blood pressure. The present study supports the hypothesis that the composition of dietary fat influences blood pressure.