The reduced respiratory muscle strength and increased work of breathing in patients with severe chronic obstructive pulmonary disease (COPD) may predispose these patients to the development of respiratory muscle fatigue and consequent respiratory failure. To test the hypothesis that these patients may be experiencing chronic respiratory muscle fatigue, we studied the effects of resting the respiratory muscles in a group of patients with severe COPD. Fifteen stable patients with severe COPD were randomized into study and control groups. In 8 study group patients (Group B), breathing was assisted with a negative pressure ventilator 3 to 6 h daily for 3 consecutive days. The remaining 7 patients served as controls (Group A) and did not receive any intervention. Baseline lung function was evaluated by spirometry and arterial blood gas determinations. Respiratory muscle strength and endurance were evaluated by maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and the maximal duration that isocapnic hyperventilation equal to 50 and 70% of the 12-s maximal voluntary ventilation could be sustained (DSV). Baseline DSV was determined as the best effort of several practice trials. All measurements were repeated on the final day of assisted ventilation approximately 2 to 3 h after its discontinuation. After assisted ventilation, the DSV at 50 and 70% of the maximal voluntary ventilation improved significantly (p less than 0.05). Maximal inspiratory pressure and MEP increased to 114% (p less than 0.05) and 112% (p = 0.05) of baseline values, respectively. Mean arterial PCO2 in the hypercapnic subgroup of Group B patients decreased from 60 mm Hg before to 52 mm Hg after assisted ventilation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)