Gas transfer in the female lung varies over the menstrual cycle in parallel with the cyclic angiogenesis that occurs in the uterine endometrium. Given that vessels form and regress in the uterus under the control of hormones, angiogenic factors and pro-angiogenic circulating bone marrow-derived progenitor cells, we tested the possibility that variation in pulmonary gas transfer over the menstrual cycle is related to a systemic cyclic pro-angiogenic state that influences lung vascularity. Women were evaluated over the menstrual cycle with weekly measures of lung diffusing capacity and its components, the pulmonary vascular capillary bed and membrane diffusing capacity, and their relation to circulating CD34⁺CD133⁺ progenitor cells, hemoglobin, factors affecting hemoglobin binding affinity, and pro-angiogenic factors. Lung diffusing capacity varied over the menstrual cycle, reaching a nadir during the follicular phase following menses. The decline in lung diffusing capacity was accounted for by ~25% decrease in pulmonary capillary blood volume. In parallel, circulating CD34⁺CD133⁺ progenitor cells decreased by ~24%, and were directly related to angiogenic factors, and to lung diffusing capacity and pulmonary capillary blood volume. The finding of greater number of lung microvessels in ovariectomized female mice receiving estrogen as compared to placebo verified that pulmonary vascularity is influenced by hormonal changes. These findings suggest that angiogenesis in the lungs may participate in the cyclic changes in gas transfer that occur over the menstrual cycle.