This study examines the effect of oral estrogen treatment on gonadotropin secretion in three young women with gonadal failure. Each subject was treated with 0.1 mg BID of ethinyl estradiol for four weeks, and the LH and FSH responses to 200 microgram of intravenously administered LHRH were measured basally and weekly during therapy. Significant reduction of basal levels of FSH occurred within one week of treatment, with obliteration of LHRH-mediated FSH responsiveness within two weeks. By contrast, basal levels of LH were significantly reduced by the end of the second week of treatment, and LHRH-mediated LH levels were sustained for three weeks. In one subject an LHRH test was performed every other day for two weeks after cessation of therapy. Return of FSH responsiveness was delayed one week beyond that of LH, which occurred within three days of discontinuation of estrogen. These results indicate that during the early phase of oral estrogen replacement therapy, FSH secretion may be selectively blunted; after discontinuation of treatment, recovery of FSH secretion lags behind recovery of LH.