Objective: To compare the effects of vaginal or oral E-2 administration on endometrial thickness, uterine perfusion, and contractility. Design: Prospective, randomized, crossover study. Setting: Assisted Reproduction Unit, Clamart, France. Patient(s): Thirty-nine infertile women undergoing 78 E-2/P cycles. Intervention(s): Women received micronized 17 beta -E-2, 2 mg/day orally (cycle days 1 to 28) and P, 300 mg/day vaginally (cycle days 15 to 28). After a menstrual cycle washout interval, women received a similar treatment except that 17 beta -E-2 was administered vaginally. Main Outcome Measure(s): Endometrial thickness, mean uterine artery pulsatility index, endometrial blood. flow, and uterine contraction frequency assessed in ultrasound scans on cycle days 14 and 18. Result(s): On day 14, the endometrium was thicker (8.7 +/- 0.6 vs. 7.1 +/- 0.3 mm, P < .0001), pulsatility index values were lower (2.4 +/- 0.1 vs. 3.0 +/- 0.2, P < .0002), and endometrial blood flow tended to be increased in the vaginal E-2 cycles as compared to the oral E-2 Cycles. On day 18, similar differences remained. However, P-induced decrease in contraction frequency was slighter in vaginal E-2 cycles (33% vs. 18%, P < .0003). Conclusion(s): Vaginal E-2 administration improves endometrial proliferation and uterine perfusion, presumably because of combined local and systemic effects, but may interfere with P-induced uterine relaxation. (C) 2001 by American Society for Reproductive Medicine.