The corpus luteum inhibiting activity of (15S)-15-methyl prostaglandin F2 alpha methyl ester (15M-PGF2 alpha) was determined when given in combination with estrogens. Administration of 15M-PGF2 alpha alone (3 injections of 500 microgram each) to monkeys concomitantly receiving hCG reduced serum progesterone concentrations to 50% of values observed in control animals. Ethinyl estradiol or mestranol alone did not inhibit the corpus luteum of the hCG-treated, nonpregnant monkey. Serum progesterone values for nonpregnant monkeys treated with 15M-PGF2 alpha plus estradiol-17 beta, ethinyl estradiol or mestranol did not differ statistically from those observed in monkeys treated with 15M-PGF2 alpha alone. The dose of 15M-PGF2 alpha (3 x 500 microgram) which only partially inhibited the corpus luteum of the hCG-treated, nonpregnant monkey promptly terminated gestation when given on Day 28 od fertile menstrual cycles. Pregnancy terminated in two of three treated monkeys when the dose of 15M-PGF2 alpha was reduced ten-fold (3 x 50 microgram). Mestranol alone reduced serum progesterone and estradiol-17 beta concentrations to one-half and one-third of pretreatment values, but did not interrupt pregnancy. Pregnancy terminated in only two of five monkeys when mestranol was administered with the low dose of 15M-PGF2 alpha. It is concluded that: 1) estrogens do not enhance the corpus luteum inhibiting of 15M-PGF2 alpha in the nonpregnant monkey; 2) the primary action of 15M-PGF2 alpha during early pregnancy is upon the conceptus and not the corpus luteum; 3) concomitant treatment with mestranol and 15M-PGF2 alpha offers no advantage of 15M-PGF2 alpha alone for the termination of early pregnancy; and 4) mestranol alone can impair the steroidogenic potential of the corpus luteum of early pregnancy, but is not sufficiently active to terminate gestation.