Asymmetrical dimethyl-L-arginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. We hypothesized that plasma levels of ADMA could be increased in patients with congenital heart disease and pulmonary hypertension. Cardiac catheterization was performed in 20 children and young adults with congenital heart disease with a median age of 10 years (range, 4 months to 33 years). The patients were assigned to group I (high flow, low pressure; n = 14) when Qp/Qs was 1.5 or greater and the mean PAP was less than 25 mm Hg or to group II (high pressure, high resistance; n = 6) when the mean PAP was greater than 25 mm Hg and Rp/Rs was greater than 0.3. Blood samples were taken from pulmonary vein or left ventricle. ADMA was measured by high-performance liquid chromatography. In addition, levels of ADMA were measured in peripheral venous blood obtained from eight control patients. Levels of ADMA in control patients (median, 0.21 microM/l; range, 0.08-0.27 microM/l) did not differ from levels obtained in group I (median, 0.30 microM/l; range, 0.06-0.49) microM/l). Patients in group II showed increased plasma levels of ADMA (median, 0.55; range, 0.25-0.79) (p < 0.01). Inhibition of nitric oxide synthase by increased levels of ADMA might contribute to pulmonary hypertension in patients with congenital heart disease.