OBJECTIVE: To assess the effects of raloxifene on the ovaries, uterus, and serum hormone levels in premenopausal women. DESIGN: Prospective study comparing pretreatment findings with findings for those on treatment. SETTING: Government research hospital. PATIENT(S): Thirty women 35 to 47 years of age who were at high risk of breast cancer and had regular, ovulatory menstrual cycles. INTERVENTION(S): Raloxifene (60 mg) and calcium (1,200 mg) daily for 2 years. MAIN OUTCOME MEASURE(S): Sonographic evidence of ovarian stimulation (>or=2 corpora lutea, or follicular cysts of >2 cm, or single follicular cyst of >3 cm). Changes in endometrial thickness, fibroid size, hormone levels, and menstrual-cycle length. RESULT(S): Fifteen subjects developed some cycles with asymptomatic ovarian stimulation, and 9 developed benign endometrial polyps, compared with 2 subjects and 1 subject pretreatment, respectively. Uterine fibroid size was unchanged during raloxifene use in 16 subjects with fibroids. On treatment, E(2) levels increased significantly only during the follicular phase, with peak E(2) levels significantly higher in cycles showing ovarian stimulation compared with those without. Sex hormone-binding globulin increased, but levels of LH, FSH, P, DHEAS, and T did not. Endometrial thickness and cycle length were unchanged. CONCLUSION(S): Premenopausal subjects receiving raloxifene showed sonographic and hormonal evidence of ovarian stimulation. Endometrial thickness, cycle length, and fibroid size were unchanged. Benign asymptomatic endometrial polyps developed in some.