To more systematically evaluate the effect of respiratory muscle rest on indices of ventilatory function, nine outpatients with stable, severe COPD were treated with nasal pressure-support ventilation delivered via a nasal ventilatory support system (BiPAP, Respironics, Inc) for 2 h a day for 5 consecutive days. An additional eight control patients were treated with sham-BiPAP. Maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), maximum voluntary ventilation (MVV), arterial blood gas values, Borg dyspnea score, dyspnea-associated functional impairment scales, and distance walked in 6 min were measured in subjects prior to and following the week-long trial. Nasal BiPAP produced a 66.3 +/- 6 percent reduction in peak integrated diaphragmatic electromyographic (EMG) activity. There were no statistically significant changes in MIP, MEP, MVV, arterial pH, PaCO2, or PaO2 or in objective measures of functional impairment from dyspnea in either group after ventilator or sham treatment. However, nasal BiPAP reduced the Borg category score during resting, spontaneous breathing from 2.0 +/- 0.4 to 0.7 +/- 0.3 (p < 0.01) after 5 days of treatment. In contrast, sham BiPAP-treated patients had no change in their dyspnea score, which was 1.8 +/- 0.4 and 1.3 +/- 0.4 before and after sham treatment, respectively. Nasal BiPAP also increased distance walked in 6 min from 780 +/- 155 to 888 +/- 151 ft (p < 0.01) (23,400 +/- 4,650 to 26,640 +/- 4,530 cm) (p < 0.01), whereas sham-BiPAP had no effect (768 +/- 96 and 762 +/- 106 ft [23,040 +/- 2,880 and 22,860 +/- 3,180 cm]) before and after sham treatment, respectively). In conclusion, these results indicate that nasal pressure-support ventilation, delivered via nasal BiPAP, improves exercise capacity and reduces dyspnea over the short term in selected outpatients with stable severe COPD. Whether such short-term improvement can be sustained merits further study.