We studied the benefits of in-hospital therapy on exercise capacity and related these changes to improvements in lung function in 17 patients with cystic fibrosis (CF) of moderate to extreme severity, as defined by results of pulmonary function tests performed at admission and discharge. Tolerance and adaptations to exercise were assessed from measures of peak work capacity (PWC), peak heart rate (PHR), and peak ventilation (PVE) obtained during an incremental exercise test. Treatment lasted from nine to 18 days. All measures of lung function improved; there also were significant increases in PWC, PHR, PVE, and PHR/PWC. Exercise-induced arterial desaturation was less at discharge than at admission. The PWC of the most severely affected patients remained abnormally low, and their adaptations to exercise were abnormal at discharge. We concluded that intensive in-hospital therapy will significantly improve exercise tolerance and lung function in patients with CF with moderate to severe pulmonary dysfunction.