The purpose of this study was to examine the hypothesis that the menstrual cycle–induced modulation of the cardiorespiratory response to exercise might be altered by acute exposure to altitude. During both the luteal and follicular phases, 9 moderately trained female subjects with normal menstrual cycles performed incremental exercise to maximal effort on a cycle ergometer at sea level (SL) and under hypobaric hypoxia (HH) at the equivalent of 3,000 m altitude. Both at rest and during exercise, minute ventilation (V˙E) and oxygen uptake (V˙O₂) did not differ between the luteal and follicular phases (either at SL or HH). However, the ratio of V˙E to V˙O₂ (V˙E/V˙O₂), both at rest and during peak exercise, was greater in the luteal phase than in the follicular phase under HH conditions. Furthermore, the partial pressure of end-tidal carbon dioxide (PETCO₂) during exercise was lower in the luteal phase than in the follicular phase in HH. These results suggest that the menstrual cycle–induced modulation of the ventilatory response to exercise may be altered under acute hypobaric-hypoxic conditions.