The effect of vitamin E on prostacyclin (PGI2) production by cultured bovine aortic endothelial cells was evaluated in vitro. We found that human plasma-derived serum (PDS) conveys a stimulatory effect on PGI2 production by cultured vascular endothelial cells. In the present study, therefore, PDS was used as a physiological stimulant for PGI2 production. There was no effect of vitamin E alone on PGI2 production without stimulation by PDS. However, simultaneous addition of vitamin E and PDS to the cultures enhanced PGI2 production in a dose-dependent manner. Furthermore, preincubation with vitamin E prior to stimulation with PDS also enhanced PGI2 production. The enhancing effect of preincubation with vitamin E was demonstrated to occur in a time- and dose-dependent manner. These results clearly indicate that vitamin E at physiological doses can enhance PGI2 production by cultured bovine aortic endothelial cells stimulated with an agent such as PDS. It seems likely that vitamin E may contribute to increase PGI2 synthesis by the vascular wall in vivo, thereby reducing platelet aggregation and thrombus formation.