A single dose of 25 mg triamcinolone acetonide, when given on day 1 or 2 of the menstrual cycle, inhibits ovulation. To examine the mechanism of this action, daily determinations of plasm FSH, LH, estrone plus estradiol (E1 + E2), and progestins were performed. Some subjects also received a single dose of LH-RH or hCG on cycle day 15 or clomiphene citrate on days 5-9. Triamcinolone acetonide itself caused variable suppression of plasma estrogens, loss of the mid-cycle gonadotropin surge, and a deficient or absent rise in plasma progestins. Impaired secretion of estrogen did not seem to be due to low gonadotropin levels. FSH and LH responses to LH-RH were adequate in relation to prevailing estrogen levels. Four of six women treated with clomiphene responded with plasma progestin levels which exceed 8 ng/ml. Triamcinolone acetonide seems to affect the hypothalamic-pituitary-ovarian axis mainly by hypothalamic suppression and possibly by a direct effect on the ovary as well.