The concept of luteal phase contraception and the use of mifepristone in clinical trials, which allows for testing of its validity, as well as clinical pharmacological research designed to understand its mode of action, are reviewed. Early luteal phase administration has a variety of morphological, physiological and biochemical effects on the endometrium that are likely to interfere with embryonic-endometrial interactions. In fact, specifically designed pilot clinical trials as well as data derived from emergency contraception studies indicate that early luteal phase administration of mifepristone is highly effective in preventing pregnancy, with minimal disturbance of hormonal parameters or menstrual cyclicity. Mid and late luteal phase administration of mifepristone at doses above 25 mg are highly effective in inducing endometrial bleeding in nonconceptional cycles. However, administration of mifepristone within the period between implantation and expected menses fails to induce bleeding in a significant proportion of cases, and furthermore the bleeding induced does not insure the termination of pregnancy. While the data suggest there is potential for a once-a-month contraceptive pill, it is likely that no molecule endowed with partial agonistic properties, like mifepristone, will completely and reliably suppress the essential functions of progesterone in order to achieve contraceptive efficacy comparable to that of modern contraceptive methods.