Sequential administration of estrogen (40 microgram depoestradiol cypionate and estradiol benzoate) on cycle days 18--20 and bromergocryptine (CB-154; 0.5 mg/kg, twice daily) on cycle days 20-22 induced luteolysis in seven of nine cynomolgus monkeys, significantly shortened menstrual cycles (23.5 +/- 0.7 days), and caused a significant decline in plasma progesterone levels during the period of CB-154 administration. Two treated monkeys did not have shortened menstrual cycles, although a luteolytic effect on plasma progesterone was evident. One monkey with a late ovulation (confirmed by endocrine parameters and laparoscopic observation) was treated with the same regimen in the early luteal phase; this also resulted in a decline in plasma progesterone and a shortened luteal phase (11 days). Treatment with the estrogen or the CB-154 component alone had no effect on menstrual cycle length or plasma progesterone levels. Similarly, treatment with CB-154 throughout the luteal phase had no effect on luteal function. An abbreviated treatment consisting of 1 day of estrogen and 1 day of CB-154 administration gave some indication of a luteolytic effect. None of these treatments produced detectable side effects. These studies have demonstrated a synergism of estrogen and CB-154 in the induction of luteolysis in cynomolgus monkeys. The present regimen, because of the effectiveness and apparent lack of side effects, deserves further investigation for possible clinical application.