We examined the effect of menstrual cycle (MC) phase on acid-base regulation and ventilatory control at rest in monophasic oral contraceptive (OC) users. Twelve healthy women (25+/-1 years; mean+/-S.E.) were tested during the inactive (IP; 5.1+/-0.2 days) and active (AP; 21.1+/-0.7 days) pill phase of the MC. Central and peripheral chemoreflex responsiveness was examined using a modified CO(2) rebreathing procedure. Minute ventilation (V E), breathing pattern and metabolic rate were measured during 10 min of quiet, resting breathing. Blood for the determination of arterial P(CO2) (Pa(CO2)) and hydrogen ion concentration ([H(+)]); plasma concentrations of the strong ion difference ([SID]) and total weak acid ([A(tot)]); serum concentrations of progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) were also obtained. Although [E(2)] (p<0.05) and [A(tot)] (p=0.05) were increased in the IP versus AP, MC phase had no significant effect on resting V E, breathing pattern, metabolic rate, [H(+)], Pa(CO2), [SID], [P(4)] and central or peripheral chemoreflex characteristics. Overall, OC had no significant physiological effect on acid-base regulation or ventilatory control at rest in healthy women. This may reflect suppression of endogenous fluctuations in circulating [P(4)] typically observed across the MC in healthy, eumenorrheic non-OC users.