The incidence of atherosclerosis and thrombosis is higher in males than in females. Gender differences in prostacyclin synthesis by rat aortic rings have been described. In this paper, sex differences in prostacyclin (PGI2, measured as 6-keto PGF1 alpha) and prostaglandin E2 (PGE2) synthesis by human endothelial cells isolated from the vein of umbilical cords are reported. Cells isolated from cords from male babies synthesized more prostacyclin and PGE2 than cells isolated from those from female babies when the cells were stimulated with 0.125 units of thrombin. The difference in PGI2 was eliminated by incubation with 0.5 units of thrombin. PGE2 synthesis was higher in males than in females using both 0.125 and 0.5 units of thrombin. Incubation of the cells with culture medium containing 20% heat inactivated plasma from either male or female subjects did not have an effect upon prostaglandin synthesis. Our results support previous evidence obtained using rat aortas and show a higher response of male cells to thrombin stimulation than that of female cells.