Exercise tolerance and cardiorespiratory adjustments at peak work capacity (PWC) were determined in 20 patients with cystic fibrosis (CF) during progressive cycle ergometry. The results were related to resting lung function tests, expressed by a pulmonary function score (PFS) that ranged from 0 (no pulmonary dysfunction) to 18 (extreme dysfunction). Patients with CF with no (PFS less than 3), mild (PFS 3-7), or moderate (PFS 8-12) pulmonary dysfunction exercised as well as normal subjects. When the PFS exceeded 12, PWC was reduced on the average by 51%, peak heart rate (PHR) was reduced by 15%, and peak ventilation (PVE) was reduced by 39%. Severely affected patients developed arterial desaturation at PWC (-7.3%), CO2 retention (end-tidal PCO2 + 5 mmHg), and an increase in the PHR/PWC ratio. In most patients with CF the PVE/PWC ratio was elevated, suggestion wasted VE and a probable increase in dead space ventilation. The results indicate that whenever pulmonary disease in CF is advanced, there are decreases in exercise tolerance and cardiorespiratory reserves, exercise-induced ventilation-perfusion abnormalities, arterial desaturation, and alveolar hypoventilation. In view of the abnormal physiological adaptations to exercise in patients with CF with advanced lung disease (PFS greater than 12), they should engage in exercise training programs and strenuous physical activity with caution and only after their cardiorespiratory reserves and adjustments to exercise have been objectively evaluated.