Noninvasive mechanical ventilation has been of use in the treatment of some forms of chronic and acute respiratory failure. However, the benefits of its use in patients in the stable phase of severe chronic obstructive pulmonary disease (COPD) remain unclear. A combination of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) may improve respiratory mechanics and alveolar ventilation, and reduce inspiratory muscle effort. In this study, we analyzed the physiologic effects of differing levels of CPAP and CPAP plus PSV in patients with stable severe COPD. Work of breathing, breathing pattern, oxygen saturation measured by pulse oximetry, PaO2, and PaCO2 were analyzed in a group of 18 patients under the following conditions: a) baseline; b) CPAP, 3 cm H20; c) CPAP, 6 cm H20; d) CPAP 3 cm H20 plus PSV 8 cm H20; and e) CPAP 3 cm H20 plus PSV 12 cm H20. CPAP at pressures of 3 and 6 cm H20 was associated with an increase in tidal volume (VT) from a mean (SD) baseline value of 0.52 (0.04) L to 0.62 (0.04) and 0.61 (0.03) L, respectively. Minute ventilation increased from 8.6 (0.5) L/min to 10.8 (0.6) and 10.9 (0.5) L/min, respectively. Mean inspiratory flow (VT/Ti) increased from 0.35 (0.02) L/s to 0.44 (0.02) and 0.41 (0.02) L/s, respectively, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) was reduced from 1.63 (0.7) cm H20 to 1.1 (0.06) and 0.37 (0.4) cm H20, respectively. CPAP did not reduce the work of breathing. Association of CPAP at 3 cm H20 with PSV of 8 or 12 cm H20 increased VT to 0.72 (0.07) and 0.87 (0.08) L, respectively, while minute ventilation increased to 12.9 (0.8) and 14.9 (1.1) L/s, respectively. Mean inspiratory flow also increased to 0.50 (0.03) and 0.57 (0.03) L/s, respectively. Work of breathing was reduced from 0.90 (0.01) J/L to 0.48 (0.06) and 0.30 (0.06) J/L, respectively, while PEEPi,dyn increased to 1.30 (0.02) and 2.42 (0.08) cm H20, respectively. With combined CPAP of 3 cm H20 and PSV of 12 cm H20, PaCO2 was reduced from a baseline value of 41.2 (1.5) mm Hg to 38.7 (1.9) mm Hg. All of the changes were statistically significant (P< .05). CPAP of 3 cm H20 in combination with PSV improved breathing pattern, increased alveolar ventilation, and reduced work of breathing. These results offer a rational basis for the use of noninvasive mechanical ventilation in the treatment of patients with stable severe COPD.