An increase in the intake of linoleic acid decreases the risk of cardiovascular disease. The mechanism for this may involve the function of linoleic acid as a prostaglandin (icosanoid) precursor. The incidence of atherosclerosis is higher in men than in women. Sex differences in prostaglandin synthesis by endothelial cells and platelets may exist. In this research work, the effects of a self-selected diet and diets with 2 levels of linoleic acid upon prostaglandin (PG) synthesis by human endothelial cells were studied, and PG synthesis by these cells when isolated from either male or female babies was compared. Prostacyclin (PG I(,2)) and PG E(,2) synthesis by endothelial cells isolated from umbilical cord veins incubated 72 hours with culture medium containing 20% plasma from women eating either, a self-selected diet, a diet with 4% (average U.S. diet) or 10% (modified diet) of energy as linoleic acid were measured by radioimmunoassay PG I(,2) as 6-keto PG F(,1)(PROPORTIONAL)). Ten subjects (half in Iowa and half in Nebraska) ate the average U.S. diet during 4 weeks, changing to the modified diet the next 4 weeks (sequence 1), and another 10 subjects followed the inverse sequence (sequence 2). PG I(,2) synthesis by cells stimulated with 0.125 units of thrombin was lower (p < 0.01) when the cells were incubated with plasma from subjects eating the diets in sequence 1. No diet effect was found when the cells were incubated with plasma from subjects eating the diets in sequence 2. PG E(,2) followed the same pattern as PG I(,2) but the differences were not significant. The per cent of linoleic acid was higher in cells incubated with plasma from subjects eating the self-selected diet and the modified diet than in cells incubated with plasma drawn when the subjects were eating the average U.S. diet. In another study, PG I(,2) and PG E(,2) synthesis by cells from umbilical cords from male babies was higher than that by cells from female babies. These differences were not changed by incubating the cells with plasma from males or females. No differences in the total fatty acid composition of the cells were found. This study supports previous reports showing that 10% compared to 4% of dietary linoleic acid either decreases or has no effect upon PG I(,2) and PG E(,2) syntheses, being both higher in males than in females.