PIP: The effect of single doses of methyltestosterone and ethinyl estradiol on the continued prothrombin depletion in Vitamin-K deficient castrate male rats was studied. 100 mcg methyltestosterone decreased prothrombin levels to 8-25% of normal plasma prothrombin values. Within 96 hours of the injection of ethinyl estradiol, plasma prothrombin levels increased from 23% to about 45%. On the basis of the effect of estradiol on prothrombin biosynthesis, it is concluded that the estrogen effect is due to a prothrombinogenic, rather than a prothrombin-sparing, mechanism.