Impaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo2) to hypoxemia, is commonly present in patients with cirrhosis. Nitric oxide (NO), through pulmonary vasodilatation, may play a major role in the oxygen abnormalities of cirrhosis. Our aim was to study the relationship between NO production and O2 abnormalities in 45 nonsmoking patients with cirrhosis and without major cardiovascular and respiratory diseases. Intrapulmonary shunting was detected by contrast-enhanced (CE) echocardiography. Lung volumes and diffusion, arterial blood gas analysis, serum NO2-/NO3-, NO output in the exhaled air, and cardiac index by the echocardiographic method were determined in all patients. Twenty-seven (60%) patients had an abnormally increased (> 15 mm Hg) AaDo2. The mean values of exhaled NO output and serum NO2-/NO3- were significantly higher in cirrhotic patients than in controls (252 +/- 117 vs. 75.2 +/- 19 nL/min/m2, P < .0001; and 47.5 +/- 29.4 vs. 32.9 +/- 10.1 micromol/L, P < .02, respectively). In all patients, there was a significant correlation between exhaled NO and AaDo2 (r = .78, P < .0001). Twelve patients (26.6%) were found to have CE-echocardiographic evidence of intrapulmonary shunting (positive CE-echo). Nine patients were considered to have hepatopulmonary syndrome (HPS) on the basis of an AaDo2 > 15 mm Hg and positive CE-echo. These 9 patients had a mean value of exhaled NO significantly higher than patients without HPS (331 +/- 73.2 vs. 223 +/- 118.4 nL/min/m2, P < .05). In all patients, cardiac index was positively correlated with exhaled NO (r = .47, P < .001) and with serum NO2-/NO3- (r = .43, P < .01). The results suggest an important role of NO in the oxygenation and circulatory abnormalities of patients with cirrhosis.