Despite improved prognosis for patients with cystic fibrosis (CF), they continue to suffer from progressive decline in pulmonary function and exercise tolerance. Beyond puberty, female patients have greater loss of pulmonary function and higher mortality than males, yet no one has studied male-female differences in exercise tolerance among patients. We therefore compared the responses to progressive exercise in 58 male and 52 female patients with CF and analyzed the influence of resting pulmonary function and gender on these responses and on breathing patterns during exercise. Within each of three pulmonary function groups (group 1: FEV1 greater than or equal to 65% predicted; group 2: FEV1 = 50-64% predicted; and group 3: FEV1 less than 50% predicted), female patients had lower exercise tolerance than males. This was reflected in the overall group for each gender: males' peak work load was 130 +/- 64 W, females' 111 +/- 32 W (P = 0.04); males' peak oxygen consumption, 36.9 +/- 11.4 mL/kg/min and females', 31.0 +/- 7.4 mL/kg/min (P = 0.0006). There was no interactive effect between gender and pulmonary function. Neither respiratory rate nor tidal volume differed between sexes. Male and female patients, irrespective of disease severity, employed similar proportions of their ventilatory capacity at exhaustion; group mean minute ventilation to maximum voluntary ventilation ratio ranged from 62.9 to 78.3%, with no apparent relationship to disease severity.