In order to further investigate the mode of action of clomiphene citrate, 5 oophorectomized women in the age range 28 to 41 years were followed with weekly determinations of serum FSH and LH for 20 weeks after the operation. They received no treatment during the first 4 weeks but during the next 16 weeks they were given estradiol 2 mg X 2 daily orally, and from the 12th to the 16th week in addition clomiphene citrate 50 mgX2 daily. The high level of FSH after the oophorectomy decreased gradually during the treatment with estradiol alone, but this effect was partly neutralized by clomiphene citrate, as we observed a significant increase in FSH within 1 week of initiating treatment with clomiphene citrate. On the other hand, we did not find any significant changes in FSH within 4 weeks after treatment with clomiphene citrate was discontinued. The high level of LH after oophorectomy did not show any significant changes during the whole treatment period. It is concluded that clomiphene citrate primarily stimulated FSH secretion, most probably by a competition with estradiol for the receptor sites in the hypothalamus or the pituitary. In addition, it is concluded that clomiphene citrate has a prolonged effect, probably because of a tight binding to the receptor sites.