The disposition of intravenously and orally administered theophylline was compared in 10 patients with cystic fibrosis (CF) and 10 healthy volunteers. The mean total body clearance of the patients with CF was twice that of the control subjects (p less than 0.001). The volume of distribution of theophylline was also greater in the patients with CF (p less than 0.05). These observations indicate that if theophylline is used in patients with CF, doses larger than those commonly given to asthmatics may be required to maintain therapeutic serum concentrations.