PIP: Roussel-Uclaf chemists and pharmacologists have developed compounds of high affinity displaying antiglucocorticosteroid and antiprogesterone activities. The most interesting derivative, RU-486 (mifepristone), was tested for both voluntary early pregnancy termination and interruption of the luteal phase in nonfertile cycles. When RU-486 was used alone in early pregnancy termination, the complete efficacy was rarely 80%. RU-486 softens and opens the cervix facilitating evacuation of the uterus; prostaglandins may be involved in this response. These results are the basis for the two step regimen currently used: RU-486 followed by prostaglandin approximately 48 hours afterwards. The efficacy of such a regimen is 95% or higher as demonstrated in about 200,000 women. The following prostaglandins are taken in conjunction with the standardized dose of 600 mg RU-486 once about 2 days before: 1) sulprostone, a PGE2 derivative at the dose of 0.25 mg administered intramuscularly, which is efficient but responsible for a few severe cardiovascular accidents; 2) gemeprost, a PGE1 derivative, in a dose of 0.5-1 mg given in a vaginal pessary; 3) misoprostol, another PGE1 derivative, is the drug of choice and it is orally active at the dose of 400-600 mcg taken in 1 or 2 ingestions; 4) 15-methyl PGF2alpha (1 or 2 injections of 50 mcg) has been used in a few countries. Misoprostol is used in combination with RU-486 for two reasons: 1) the RU-486 plus misoprostol regimen is prescribed by practicing gynecologists in their office; 2) it is possible to envisage a one-step, simplified mode of administration because of both the safety and convenience of the method. For example, when women seek pregnancy termination, the physician could give RU-486 and a few pills of misoprostol to be taken 48 hours later. Other uses of prostaglandins associated with RU-486 include: 1) therapeutic pregnancy interruption late in the first trimester and afterwards; 2) the use of RU-486 to induce labor when there is abnormally prolonged pregnancy, particularly if there is cervical dysfunction; and 3) the use of RU-486 at the end of the cycle has been proposed for induction of menses.