This study was conducted to assess to what extent the Yuzpe regimen, or half the dose, given in the follicular phase, prevents ovulation during the ensuing 5 days. Sixty women were divided into six groups. All groups received placebo in one cycle and drug in another, in a randomized order. Groups differed by the dose and size of the leading follicle at the time of treatment (12-14, 15-17, or 18-20 mm). Ovulation was absent during the ensuing 5 days in 13 of 20 participants (65%) and in 8 of 20 participants (40%) who received the full and the half dose, respectively, when follicles were 12-17 mm. No ovulation occurred, within the critical period, in 7 of 39 placebo cycles (18%). When follicles were 18-20 mm, treatment did not prevent ovulation. In most drug-treated cycles, plasma gonadotropin and sex steroid levels were significantly depressed within the 5-day period, even when follicular rupture occurred within that period. In conclusion, the Yuzpe regimen can suppress or postpone ovulation to an extent that exceeds the fertile life of spermatozoa. Lack of ovulation within the critical period and dysfunction of the ovulatory process probably account for the contraceptive effect of this method in most cases. The present data do not warrant the use of half the dose of the Yuzpe regimen.