A single dose of mifepristone is an effective emergency contraceptive and has potential as a regular "once-a-month" pill. If given in the early luteal phase, the formation of a secretory endometrium is inhibited or delayed and implantation of the embryo prevented. We have explored the effect of giving the mifepristone just prior to ovulation on the ovarian and endometrial cycle. Seven women with regular menstrual cycles were studied during a control cycle and then in a second cycle when 200 mg mifepristone was given within 24 h of ovulation, i.e., when luteinizing hormone (LH) in serum was >15 IU/L and the dominant follicle was >18 mm. Ovulation was confirmed within 48 h by ultrasound in five of the seven women. The remaining two women had luteinized unruptured follicle. Following mifepristone, menses occurred after a normal luteal phase compared to control cycle (13.7 +/- 0.7 vs. 13.7 +/- 0.9 days). In all subjects the endometrium on LH + 6 in the treatment cycle showed no, or very little, secretory changes, suggesting it was unlikely that pregnancy would have occurred. We conclude that mifepristone could be given as a "once-a-month" contraceptive pill without causing significant disruption in the menstrual cycle in the majority of women for a 4-day period from just prior to ovulation until LH + 3.