To examine whether changes in respiratory chemosensitivity during the menstrual cycle are related to worsening of airway functions, hypoxic and hypercapnic ventilatory and P0.1 responses, airway function, and serum progesterone levels were studied in 11 female asthmatic patients in both the follicular and luteal phases. Plasma progesterone levels were 30-fold higher in the luteal phase than in the follicular phase (p < 0.0001). The PaCO2 decreased from 37.1 +/- 0.98 (SE) mm Hg to 35.1 +/- 0.89 mm Hg (p = 0.05) and HCO3- decreased from 22.4 +/- 0.44 mEq/L to 20.8 +/- 0.61 mEq/L (p < 0.001), from the follicular phase to the luteal phase, respectively. From the follicular to the luteal phase, delta VE/delta PACO2 tended to increase from 1.57 +/- 0.12 L/min/mm Hg to 1.91 +/- 0.26 L/min/mm Hg (p = 0.08) and delta P0.1/delta PACO2 increased from 0.25 +/- 0.05 cm H2O/mm Hg to 0.37 +/- 0.08 cm H2O/mm Hg (p = 0.05). During hyperoxic hypercapnia in the luteal phase, VE, f, and mean inspiratory flow increased and TI and TE decreased (p < 0.05). There were no differences in the hypoxic ventilatory and P0.1 responses and airway functional parameters (FEV1, PEF, V50, V25, and Raw) of the two phases. The increases in hypercapnic ventilatory and P0.1 responses were correlated to the improvement in FEV1 and PEF (p = 0.05 and p < 0.01, respectively). These results suggest that, although there is an augmentation of hypercapnic chemosensitivity during the luteal phase in female asthmatic patients, this is not associated with the decline in airway functions.