ERA-923 is a new selective estrogen receptor modulator under clinical investigation for use in tamoxifen refractory metastatic breast cancer. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-daily oral ERA-923 (10-200 mg) for 28 days in healthy postmenopausal females. ERA-923 was well tolerated, and adverse events were mild and reversible. No clinically significant changes in laboratory values were found with ERA-923 versus placebo. ERA-923 appeared to undergo extensive metabolism and enterohepatic recirculation. In addition, pharmacokinetic analysis showed that a high-fat breakfast increased the extent of absorption. ERA-923-dosed subjects had no uterine or ovarian changes when evaluated with transvaginal ultrasound and compared to placebo subjects. Overall, ERA-923 was safe and well tolerated in postmenopausal women dosed for 28 days.