OBJECTIVE To assess uterine artery blood flow and endometrial thickness in postmenopausal patients receiving sequential hormone replacement therapy (HRT) at different phases of the treatment. METHODS Prospective controlled study. METHODS Ultrasound and menopause units of the obstetrics and gynecology department of the University of Tor Vergata, Rome, Italy. METHODS Forty postmenopausal women were treated with cyclic sequential HRT (transdermal E2, 50 microg/d, days 1-21; and dydrogesterone, 10 mg/d, days 12-24). METHODS All patients underwent transvaginal color Doppler sonography in the estrogen (phase E) and progestogen (phase E/P) phases and after uterine bleeding when no hormone was administered (phase 0). METHODS Endometrial thickness; systolic, diastolic, and mean velocities; and pulsatility and resistance indices of the uterine arteries. RESULTS No statistically significant difference in endometrial thickness between phase E (6.5+/-1.6 mm) and phase E/P (6.0+/-1.7 mm) was observed. In phase 0, compared with phases E and E/P, a statistically significant decrease in endometrial thickness was found (4.1+/-1.2 mm). Doppler flow impedance parameters of uterine arteries during the different phases of the HRT cycle showed no differences between the phases considered. CONCLUSIONS The decrease in endometrial thickness in phase 0 suggests a protective effect of our cyclic sequential regimen on the endometrium. Dydrogesterone does not interfere markedly with the vasodilatory effect of estrogen on uterine arteries.