The hyperdynamic circulation of cirrhosis and portal hypertension has been postulated to be due to the vasodilatory effects of nitric oxide. However, there have been conflicting results in adults and no studies in children. We aimed to measure the nitric oxide level in serum of pediatric patients with portal hypertension with and without cirrhosis, in order to assess its role in the development of hemodynamic changes. We measured nitric oxide levels in 41 pediatric patients (21 patients with intrahepatic portal hypertension and 20 with extrahepatic portal hypertension). The mean age of the study population was 11.2 +/- 4.6 years; 53 per cent were female. Twenty healthy children were included as a control group. Nitric oxide levels were measured by Boehringer-Mannheim colorimetric assay and the statistical significance was calculated by Kruskal-Wallis one-way ANOVA. Significantly higher nitric oxide levels were found in patients independent of the type of portal hypertension compared with the control group (29.4 +/- 6 in patients with intrahepatic portal hypertension, 29.5 +/- 5.8 in patients with extrahepatic portal hypertension, and 23.6 +/- 6.5 in the control group; p < 0.007). These data showed a difference between the groups and suggest that nitric oxide, predominantly independent of cirrhosis, plays a primary role in the pathogenesis of portal hypertension.