Platelet lipid biosynthesis in relation to aggregation has been studied in female rats treated with ethynylestradiol and fed laboratory chow or a vitamin E-deficient diet. In both normal and vitamin E-deficient rats, administration of ethynylestradiol highly significantly (p less than .001) increased the biosynthesis of total lipids but mostly of lanosterol (+ dihydrolanosterol) by thirteen-fold in normal rats and by nine-fold in vitamin E-deficient rats. The increased lipid synthesis was associated with a higher response of platelets to thrombin-induced aggregation. Concomitant administration of alpha-tocopherol acetate in both normal and vitamin E-deficient rats depressed markedly the enhanced lipid synthesis and aggregation induced by estrogen. Administration of ethynylestradiol lowered considerably the level of vitamin E in plasma but not in platelets. Treatment by tocopherol partly corrected the low plasma level of vitamin E resulting from estrogen administration. In vitro addition of lanosterol to platelets highly significantly increased the response of platelets to thrombin- and ADP-induced aggregation. This hyperaggregability was almost entirely inhibited by preincubation of platelets with tocopherol acetate. In the present in vivo and in vitro studies, alpha-tocopherol was able to neutralize most of the adverse effects of estrogen on blood platelets.