Various progestogens were given to postmenopausal and premenopausal women. The first group consisted of 46 postmenopausal patients and in the postmenopausal atrophic smear, 17 acetoxyprogestogens produced no effect. However, the administration of two 19 nortestosterone derivatives, ethynodiol diacetate and norethisterone increased the Karyopyknotic Index and degree of proliferation of the epithelium, presumably due to their estrogenic metabolites. Low grade hypotrophic smears, consisting of parabasal and intermediate cells, reacted by a decrease in the size of the intermediate cells associated with clumping, and a disappearance from the smear of parabasal cells. In the case of ethynodiol diacetate, its estrogenic effect of elevating the Karyopyknotic Index occurred before the progestogenic effect of clumping and fusing of the intermediate cells. The second group consisted of 370 women using an oral form of sequential contraception, based on administration of 0.05 mg ethinyl estradiol daily for three weeks followed by a combined oral contraceptive containing the same amount of estrogen with varying progestogens for a further week. The anti-estrogenic effect of the various progestogens was then compared by their ability to lower the Karyopyknotic Index. This levelled out after four or five tablets. The most potent progestogen was d-norgestrel in the lowest dose of 0.25 mg and this compound exerted a greater effect than 4 mg norethisterone, 1 mg ethynodiol diacetate or 4 mg megestrol acetate.