Inhaled nitric oxide (NO) has been shown to reduce the mean pulmonary artery pressure (mPAP) and to improve PaO2 in patients with acute respiratory failure undergoing oxygen (O2) therapy. However, inhaled NO reduced pulmonary hypertension without improving PaO2 in patients with chronic obstructive pulmonary disease (COPD). This study was intended to compare the hemodynamic and gas exchange responses during inhalation of NO or O2 with those observed during the combined inhalation of NO and O2 in 10 spontaneously breathing COPD patients. Hemodynamic and blood gas parameters were measured after breathing: (1) room air; (2) NO added to room air; (3) O2 (1 L/min); or (4) NO and O2. During inhalation of 2 ppm NO added to room air, the mPAP (23.1 +/- 2.5 versus 20.6 +/- 2.2 mm Hg) and the pulmonary vascular resistance (PVR) (434 +/- 70 versus 378 +/- 50 dyne s/cm5) were significantly (p < 0.05) lower than those measured with room air. However, the values of PaO2 did not improve. The combined inhalation of NO and O2 was associated not only with a significant (p < 0.05) decrease of mPAP (21.4 +/- 2.3 versus 19.7 +/- 1.8 mm Hg) and PVR (431 +/- 72 versus 370 +/- 44 dyne s/cm5), but also with a remarkable improvement (p < 0.05) in the values of PaO2 (91.4 +/- 6.6 versus 111.5 +/- 7.8 mm Hg) as compared with values obtained during the inhalation of O2 alone. These findings suggest that combined therapy with NO and O2 may constitute an alternative approach to treating patients with COPD and pulmonary hypertension.