The effect of tamoxifen on the growth of endometrial implants was examined in rats with experimentally induced endometriosis. Administration of tamoxifen (1 mg/kg x day) for 60 days completely regressed the endometrial implants. When tamoxifen treatment was withdrawn, recurrence of endometrial implants was observed. Ectopic endometrial implants regressed completely 2 months after ovariectomy in rats with experimentally induced endometriosis. Tamoxifen administration (1 mg/kg x day) for 60 days to ovariectomized rats with regressed implants led to complete recurrence of ectopic endometrial implants. In ovariectomized rats administration of tamoxifen antagonized estradiol-enhanced thymidine incorporation into uterine DNA, but tamoxifen per se stimulated thymidine incorporation. This indicates the agonist/antagonist nature of tamoxifen. Treatment of rats with tamoxifen blocked the normal estrous cycle. However, serum progesterone levels were higher during tamoxifen treatment in rats with intact ovaries than in ovariectomized rats. When ovariectomized rats with regressed implants were administered tamoxifen (1 mg/kg x day) and progesterone (10 mg/kg x day) for 60 days, recurrence of ectopic endometrial implants was not observed. These findings suggest that tamoxifen is effective in regressing endometrial implants in rats with experimentally induced endometriosis, and ovarian progesterone may have a facilitatory effect.