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. Design: Prospective controlled study. Setting: Ultrasound and menopause units of the obstetrics and gynecology department of the University of Tor Vergata, Pome, Italy. Patient(s): Forty postmenopausal women were treated with cyclic sequential HRT (transdermal E-2, 50 mu g/d, days 1-21: and dydrogesterone, 10 mg/d, days 12-24). Intervention(s): 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). Main Outcome Measure(s): Endometrial thickness: systolic, diastolic, and mean velocities; and pulsatility and resistance indices of the uterine arteries. Result(s): No statistically significant difference in endometrial thickness between phase E (6.5 +/- 1.6 mn) 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 Row impedance parameters of uterine arteries during the different phases of thr HRT cycle showed no differences between the phases considered. Conclusion(s): 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. (Fertil Steril(R) 1999;71:536-43. (C) 1999 by American Society for Reproductive Medicine.)