The pharmacokinetics and metabolic conversion of the ethynylated estrogens are reviewed. Special emphasis is given to the comparative pharmacokinetics of ethynylestradiol in different populations of women. Similarly, the variability of ethynylestradiol and mestranol metabolism in humans resulting from presentation of radio‐labeled steroid and purification of the metabolic products is presented and discussed. The concepts of estrogen hepatotoxicity are reviewed with respect to the known phenomenon of estrogen oxidative metabolism and covalent binding. Recent evidence for the metabolic removal of the 17α‐ethynyl group is discussed, and its relationship to estrogen hepatoxicity is considered and related to the covalent binding phenomenon.