This study examined the effects of menstrual cycle phase on ventilatory control. Fourteen eumenorrheic women were studied in the early follicular (FP; 1-6 days) and mid-luteal (LP; 20-24 days) phase of the menstrual cycle. Blood for the determination of arterial PCO(2) (PaCO(2)) , plasma strong ion difference ([SID]), progesterone ([P(4)]), and 17beta-estradiol ([E(2)]) concentrations were obtained at rest. Subjects performed a CO(2) rebreathing procedure that included prior hyperventilation and maintenance of iso-oxia to evaluate central and peripheral chemoreflex, and nonchemoreflex drives to breathe. Resting PaCO(2) and [SID] were lower; minute ventilation (V (E)), [P(4)] and [E(2)] were higher in the LP versus FP. Within the LP, significant correlations were observed for PaCO(2) with [P(4)], [E(2)] and [SID]. Menstrual cycle phase had no effect on the threshold or sensitivity of the central and/or peripheral ventilatory chemoreflex response to CO(2). Both (V (E)) and the ventilatory response to hypocapnia (representing nonchemoreflex drives to breathe) were approximately 1L/min greater in the LP versus FP accounting for the reduction in PaCO(2) . These data support the hypothesis that phasic menstrual cycle changes in PaCO(2) may be due, at least in part, to the stimulatory effects of [P(4)], [E(2)] and [SID] on ventilatory drive.