Two experiments were conducted to determine how RU486 affected oestradiol action in the non-human primate female reproductive tract. In the first experiment, spayed rhesus monkeys were first treated with a sequential regimen of oestradiol and progesterone to cause regression and deciliation in the oviduct and progestational development in the endometrium. The ability of oestradiol to stimulate oviductal differentiation and endometrial regeneration in the presence of RU486, progesterone, and progesterone plus RU486 was then tested. RU486 was found to block the ability of oestradiol to increase endometrial growth but did not prevent oestradiol-dependent oviductal differentiation. Also, in the endometrium but not the oviduct, RU486 action differed from simple progesterone withdrawal by causing stromal compaction and glandular apoptosis. In the second experiment, spayed monkeys were first treated with oestradiol for 2 weeks to produce a fully differentiated, ciliated-secretory oviduct and an hypertrophied, proliferative endometrium. The ability of oestradiol to maintain these conditions in oviduct and endometrium during treatment with RU486, progesterone, and progesterone plus RU486 was then tested. It was found that RU486 suppressed the ability of oestradiol to maintain the endometrium in a hypertrophied state but not its ability to maintain the oviduct in a fully ciliated-secretory state. As before, RU486 induced extensive glandular apoptosis and stromal compaction in the endometrium, but not the oviduct. These endometrial effects appeared to be due to a combination of a decrease in proliferation, an increase in epithelial cell death by apoptosis, an increase in stromal compaction and a concomitant decrease in interstitial fluid content, all of which led to a decrease in endometrial wet weight and thickness. These effects of RU486 on oestradiol action were similar in the presence and absence of progesterone and were therefore separate and distinct from the classical antiprogestin effects of RU486. Because RU486 did not inhibit the ability of oestradiol to either stimulate or maintain oviductal differentiation or wet weight, these results suggest that the endometrium is much more sensitive to the anti-proliferative effects of RU486 than the oviducts.