PIP: A study of the effect of combination oral contraceptives upon endogenous ovarian estrogen production was done by measuring serum estradiol levels in 3 groups of women. The first group of 3 women gave daily serum samples during 1 control and 2 treated cycles (2 mg. norethindrone and 100 mu-g mestranol received daily for 20 days), and levels of follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were measured. A second group (6) taking oral contraceptives for at least a year were measured daily during 1 cycle for estradiol only. Each of 97 women in the third group, taking the pill from 1 to 6 years, gave a single blood sample taken at random during the cycle, to be assayed for estradiol. Estradiol levels in women receiving oral contraceptives were low, usually in the range of 20-30 pg./ml., similar to those found in the early follicular phase in ovulatory cycles, and significantly higher than levels found in postmenopausal women. Exogenous estrogen in the pill, together with this level of endogenous estradiol, should be sufficient to prevent any harmful effects associated with estrogen deficiency. The finding that estradiol levels remain low in the first cycle of therapy is consistent with previous studies which indicate that one of the mechanisms of action of hormonal contraceptives is a direct effect upon the ovary.