OBJECTIVE--To evaluate whether circulating endothelin, a peptide that is thought to play a part in mediating vascular tone, might be high in pulmonary hypertensive congenital heart disease. DESIGN--A prospective study with a radioimmunoassay technique to estimate urinary and plasma endothelin concentrations. SETTING--A supraregional referral centre for patients with congenital heart disease. PATIENTS--The 12 hour urinary endothelin concentration in young children with an increased pulmonary blood flow (n = 24, median age eight months) were compared with those in children with right ventricular outflow tract obstruction (n = 14, median age 1.5 years) and with those in healthy controls (n = 16, median age 1.8 years). The concentrations were also measured in adolescents with irreversible pulmonary vascular disease (n = 17, median age 18 years) and compared with those in controls of similar age (n = 19, median age 18.5 years). Also the plasma concentrations in the left atrium and pulmonary artery were measured in young children with either high (n = 11, median age 10.8 months) or low (n = 5, median age 1.0 year) pulmonary blood flow, in the peripheral arterial and venous blood of young children with either high (n = 13, median age 10.8 months) or low (n = 6 median age 1.9 years) pulmonary blood flow, and in the peripheral venous blood of seven healthy young children (median age 1.7 years). RESULTS--The urinary excretion of endothelin was similar in young children of a similar age, whether they had high, low, or normal pulmonary blood flow. Also, urinary endothelin excretion in older patients with irreversible pulmonary vascular disease was similar to that in normal subjects of similar age. Urinary endothelin excretion in normal young children, however, was significantly greater than that in normal older subjects (p = 0.0001). There was no transpulmonary or arteriovenous difference detected in either children with high or low pulmonary blood flow, and plasma concentrations sampled from the left atrium, pulmonary artery, and systemic artery and vein were similar in both groups. CONCLUSION--There was no evidence to implicate circulating endothelin in the pathogenesis of pulmonary vascular disease.