Recent investigations have shown that theophylline improves diaphragmatic contractility of the respiratory muscles in isolated muscle preparations in animals and in normal human subjects. It has also been demonstrated that theophylline can reverse diaphragmatic fatigue and prevent fatigue of the diaphragm when given prophylactically. These effects have also been demonstrated in patients with severe chronic obstructive pulmonary disease, all of whom retained CO2 (PaCO2 53 +/- 3 mm Hg) and had hypoxia (PaO2 57 +/- 8 mm Hg). Theophylline, which increases respiratory muscle strength and delays the onset of diaphragmatic fatigue therefore could be a very useful agent in the treatment of patients with chronic airway obstruction.