Estrogen administration during the luteal phase of the menstrual cycle has been shown to be luteolytic, but the exact mechanism is unknown. Since estrogen inhibits LH [lutropin] release, causes a release of prostaglandin F2.alpha. (PGF) and acts directly on the corpus luteum to lower progesterone (P), the possibility exists that estrogen''s mechanism of action is mediated by any 1 or all of these effects. The acute effects of 17.beta.-estradiol (E) administration on LH release, on P secretion by the corpus luteum and on the release of PGF from the primate ovary were investigated. Normally cycling monkeys were selected on days 19-20 of the cycle (5-7 days after the periovulatory estradiol surge). Under general anesthesia, the ovarian vein ipsilateral to the corpus luteum was cannulated, and blood was collected on ice at 20 min intervals for 4 h [1 h before treatment (control) and 3 h during treatment]. The animals were randomly divided into 4 experimental groups: control (vehicle treatment), estradiol (1 ng/min i.v. for 3 h), estradiol-indomethacin (15 ng/kg indomethacin i.m. followed by estradiol, as above) and indomethacin (15 ng/kg i.m., followed by estradiol-vehicle). A peripheral vein sample was taken at the start and at the conclusion of each experiment, and the blood was analyzed for LH, PGF, P and E by RRIA [radioimmunoassay]. Vehicle treatments had no effect on ovarian and peripheral LH, PGF, P or E. E infusion lowered ovarian and peripheral P and raised PGF without any change in LH. Indomethacin blocked the P decrease caused by E without any significant change in LH values. The mechanism of estradiol-induced luteolysis in the rhesus monkey may be mediated through intraovarian PGF.