We studied a maximum fall in VE (max delta VE) produced by 20 sec O2 breathing and its percentage of resting VE (reflex hypoxic drive) on 9 menstruating women, in order to examine menstrual phase effect on reflex hypoxic drive. During the luteal phase, resting PAO2 was higher by 4.8 mm Hg and PACO2 was lower by 3.0 mm Hg than during the follicular phase. In spite of these changes in the alveolar gases, reflex hypoxic drive was greater in the luteal phase (14.4%) than in the follicular phase (9.3%). Resting VE in the luteal phase was 7.8% greater than that in the follicular phase. Contribution of the augmented hypoxic drive to the increased resting VE in the luteal phase, calculated as delta (max delta VE)/delta VE (%), was 59 +/- 29% (mean +/- SE). These results suggest that progesterone-induced hyperventilation, as occurs in the luteal phase, is elicited partly by mediating an increase in reflex hypoxic drive which is probably produced centrally even in hyperoxia and hypocapnia, but the role of augmented hypoxic drive is highly variable among subjects.