The effects of postcoital d-norgestrel, in an oral dose of 400 mcg were studied in healthy, fertile women who had normal ovulatory menstrual cycles. Plasma LH showed alteration even with doses of only 1 to 3 tablets per cycle. However, midcycle peaks were usually not abolished, and coexisted with normal urinary pregnanediol levels. The pregnanediol values were not affected by doses of less than 5 tablets per cycle, but were inhibited by larger doses. At the genital level, the action of one single dose began 3 h after ingestion, as indicated by modification of the cervical mucus. Such action increased and reached the maximum at 9 h. Intracervical penetration by the sperm was not influenced until the medication had been active for 7 h. The results of the intrauterine sperm recovery tests indicated that despite normal initial penetration, the sperm disappeared from the intrauterine fluid in proportion to the activity of the medication. Intrauterine pH showed constant alkalinization, which began at 4 h after ingestion of the dose, and was accompanied by rapid disappearance of living sperm from the uterine cavity. Alteration of the genital environment and consequent interference with ascent of the sperm might have a role in the contraceptive mechanism of postcoital d-norgestrel.