We investigated the cardiovascular responses to acute hypercapnia during the menstrual cycle. Eleven female subjects with regular menstrual cycles performed hypercapnic rebreathing tests during the follicular and luteal phases of their menstrual cycles. Ventilatory and cardiovascular variables were recorded breath by breath. Serum progesterone and estradiol were measured on each occasion. Serum progesterone was higher during the luteal [50.4 +/- 9.6 (SE) nmol/l] than during the follicular phase (2.1 +/- 0.7 nmol/l; P < 0.001), but serum estradiol did not differ (follicular phase, 324 +/- 101 pmol/l; luteal phase, 162 +/- 71 pmol/l; P = 0.61). The systolic blood pressure responses during hypercapnia were 2.0 +/- 0.3 and 4.0 +/- 0.5 mmHg/Torr (1 Torr = 1 mmHg rise in end-tidal PCO2) during the follicular and luteal phases, respectively, of the menstrual cycle (P < 0.01). The diastolic blood pressure responses were 1.1 +/- 0.2 and 2.1 +/- 0.3 mmHg/Torr during the follicular and luteal phases, respectively (P < 0.002). Heart rate responses did not differ during the luteal (1.7 +/- 0.3 beats.min-1.Torr-1) and follicular phases (1.4 +/- 0.3 beats.min-1.Torr-1; P = 0.59). These data demonstrate a greater pressor response during the luteal phase of the menstrual cycle that may be related to higher serum progesterone concentrations.