BACKGROUND--In vitro studies have suggested an important role for the endothelium in the control of pulmonary vascular tone, but endothelium dependent and independent relaxation of pulmonary arteries have not been studied in children in vivo. METHODS--The response of the pulmonary circulation to graded infusions of acetylcholine (an endothelial dependent vasodilator) and to nitroprusside (a dilator not dependent on endothelium) was studied in 10 children aged four to 16 years who had normal pulmonary haemodynamics. Arterial diameter was measured by quantitative angiography, and pulmonary blood flow velocity was measured with a 3F intra-arterial Doppler catheter placed in a lower lobe segmental artery. RESULTS--There was a dose dependent increase in flow velocity in response to acetylcholine (maximum response 93%) (SEM 7%), and an increase of 51% (8%) in response to nitroprusside. By contrast, segmental artery diameter was unchanged during acetylcholine infusion in all patients, and increased only modestly in response to nitroprusside (5% (1%)). CONCLUSIONS--The most important site of action of endothelium dependent and independent pulmonary vasodilators is distal to the segmental pulmonary arteries. Despite low resting tone in the pulmonary circulation, endothelium dependent vasodilatation can be shown in vivo. This may allow study of the role of endothelial dysfunction in children with abnormal pulmonary haemodynamic secondary to congenital heart disease.