Possible mechanisms of action of a combination of ethinylestradiol (EE) and dl-norgestrel as a postcoital contraceptive agent were studied in 12 healthy female volunteers. An oral dose of 0.1 mg of EE and 1.0 mg of dl-norgestrel was given at the predicted time of ovulation and again 12 hours later. Serum luteinizing hormone, prolactin, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by specific radioimmunoassays in blood samples obtained daily from the 8th day of the menstrual cycle to the 1st day of menses. Hormone profiles suggested that the medication elicited a range of individual variations in pituitary and/or ovarian responses. Histologic examination of the endometrium consistently showed significant alteration in endometrial development with a dissociation in maturation of glandular and stomal components. This postcoital contraceptive acts either by (1) suppressing ovulation or (2) disrupting luteal function by acting directly on the corpus luteum or by interfering with appropriate endometrial responses to ovarian steroids.