The effectiveness of a combination of RU 486, an antiprogestin, and epostane, a 3 beta-hydroxysteroid dehydrogenase inhibitor, for termination of pregnancy in female rats was determined. Epostane administered at doses ranging from 8 to 48 mg/Kg/day on days 7, 8, and 9 of pregnancy did not influence the progress of the pregnancy. RU 486 in doses of 1, 2, and 4 mg/Kg/day terminated pregnancy in 0, 40, and 100% of rats, respectively. The combination of epostane (48 mg/Kg/day) plus RU 486 (1 and 2 mg/Kg/day) terminated pregnancy with complete resorption of fetuses in all treated animals. Unexpectedly, the drug combination that terminated pregnancy used a dose of epostane that was not highly effective in lowering serum progesterone levels when epostane was administered alone. Thus, in the rat, the synergistic action of epostane plus RU 486 may not be dependent upon reduced progesterone secretion plus receptor blockage as anticipated. The present results suggest that the combination of epostane plus RU 486 is effective for pregnancy termination.