Although a fall in arterial oxygen saturation (SaO2) during exercise has been reported in patients with advanced lung disease due to cystic fibrosis (CF), not every patient with advanced disease desaturates, and pulmonary function tests have not been considered predictive as to which patient will desaturate. This study evaluated oxygen desaturation by ear oximetry during a progressive exercise test in 21 patients with CF and compared it to forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and the single breath diffusing capacity for carbon monoxide (DCO), all expressed as percent predicted. During exercise, the SaO2 fell less than 0.25 percent per ml of the maximal O2 consumption per kilogram of body weight to values never less than 90 percent in 15 patients (group A), whereas it fell more than this and always to values at the end of exercise of less than 90 percent in six others (group B). The FEV1 ranged from 103 percent predicted to 37 percent for group A compared to 28 to 17 percent in group B, while the range of FEV1/FVC was 87 to 52 percent for group A and 54 to 40 percent for group B. The range of DCO for group A was 129 to 84 percent compared to 64 to 54 percent. In conclusion, this study found that both the FEV1 and the DCO could separate those that had significant desaturation from those that did not and that no patient with a DCO of 80 percent or greater had significant desaturation during exercise.