Sleep studies were performed in 20 clinically stable cystic fibrosis (CF) patients (mean age, 18.2 years) to determine the magnitude of fall in hemoglobin saturation (Sao2) during sleep and to relate these changes to pulmonary function and echocardiographic findings. Five healthy young adults served as controls. In both groups, the maximum fall in Sao2 was seen during rapid eye movement (REM) sleep. The mean maximum fall in the control group during REM sleep was 2.0% (range, 1% to 3%), compared with 7.4% (range, 1% to 23%) in the CF group. Of the 11 patients in whom right ventricular systolic time intervals were obtained, eight of the nine patients with falls in Sao2 greater than 3% during REM sleep had echocardiographic evidence of pulmonary hypertension. Repeated episodes of desaturation during sleep may contribute to the development and progression of cor pulmonale in CF patients.