Using low doses of vitamin E, either in vitro or in vivo, we have succeeded in almost doubling plasma and platelet alpha-tocopherol in healthy humans. Despite such an enrichment, platelet aggregation induced by collagen and thromboxane A2 minetic U46619 was not much affected, although that induced by exogenous arachidonic acid was significantly decreased. Similarly, the oxygenation of exogenous arachidonic acid was not modified. When incubated with thrombin some variations in the formation of endogenous cyclooxygenase and lipoxygenase products could be observed, although rarely significantly. The tendency was a decrease after in vivo enrichment and an increase when enrichment occurred in vivo. Serum oxygenated metabolites of arachidonic acid as well as urinary metabolites of thromboxane and prostacyclin were also not affected after vitamin E supplementation. Since the lipoxygenation of eicosapentaenoic acid was very strongly peroxide-dependent, the effect of alpha-tocopherol enrichment was tested and the 12-hydroperoxide derivative of arachidonic acid was used as a physiological peroxide. No modification could be observed, confirming that vitamin E does not alter the specific peroxidation of polyunsaturated fatty acids in normal platelets. We conclude that vitamin E supplementation neither affects arachidonic acid-dependent aggregation nor the oxygenated metabolism of arachidonic acid in normal human platelets.