OBJECTIVES. We compared the ability of inhaled nitric oxide (NO), oxygen (O-2) and nitric oxide in oxygen (NO+O-2) to identify reactive pulmonary vasculature in pulmonary hypertensive patients during acute vasodilator testing at cardiac catheterization. BACKGROUND. In patients with pulmonary hypertension, decisions regarding suitability for corrective surgery, transplantation and assessment of long-term prognosis are based on results obtained during acute pulmonary vasodilator testing. METHODS. In group 1, 46 patients had hemodynamic measurements in room air (RA), 100% O-2, return to RA and NO (80 parts per million [ppm] in Rtl). In group 2, 25 additional patients were studied in RA, 100% O-2 and 80 ppm NO in oxygen (NO+O-2). RESULTS. In group 1, O-2 decreased pulmonary vascular resistance (PVR) (mean +/- SEM) from 17.2 +/- 2.1 U.m(2) to 11.1 +/- 1.5 U.m(2) (P < 0.05). Nitric oxide caused a comparable decrease from 17.8 +/- 2.2 U.m(2) to 11.7 +/- 1.7 U.m(2) (p < 0.05). In group 2, PVR decreased from 20.1 +/- 2.6 U.m(2) to 14.3 +/- 1.9 U.m(2) in O-2 (p < 0.05) and further to 10.5 +/- 1.7 U.m(2) in NO+O-2, (p < 0.05). A response of 20% or more reduction in PVR was seen in 22/25 patients with NO+O-2 compared with 16/25 in O-2 alone (p = 0.01). CONCLUSIONS. Inhaled NO and O-2 produced a similar degree of selective pulmonary vasodilation. Our data suggest that combination testing with NO+O-2 provides additional pulmonary vasodilation in patients with a reactive pulmonary vascular bed in a selective, safe and expeditious fashion during cardiac catheterization. The combination of NO+O-2 identifies patients with significant pulmonary vasoreactivity who might not be recognized if O-2 or NO were used separately.(C) 1999 by the American College of Cardiology.