Serotonin (5HT) is a potent vasoconstrictor of the pulmonary vascular bed and may be involved in the pathophysiology of secondary pulmonary hypertension in children with a left-to-right shunt due to a congenital heart defect. To test this hypothesis we measured the total and free 5HT concentration in blood as well as the urinary excretion of its main metabolite 5-hydroxyindoleacetic acid (HIAA) in children showing a left-to-right shunt with (n = 10) and without (n = 18) pulmonary hypertension. 5HT and HIAA were also measured in children after corrective cardiac surgery using cardiopulmonary bypass (n = 14) and in controls without congenital heart disease (n = 18). The concentrations of total and free 5HT were not significantly different between controls and patients with a left-to-right shunt. After cardiac surgery total 5HT concentration was significantly reduced by about 65% owing to a postoperatively reduced platelet count. In patients with a left-to-right shunt the total 5HT content was similar in the right atrium (204.0 +/- 17.3 ng/ml), pulmonary artery (189.0 +/- 19.1 ng/ml), and aorta (195.0 +/- 19.3 ng/ml), as was the free 5HT concentration. Therefore no net release of 5HT from platelets occurred between these sampling sites. In patients with pulmonary hypertension, the urinary excretion of HIAA was significantly increased when compared with controls and patients without pulmonary hypertension. It is concluded that turbulent blood flow in children with a left-to-right shunt does not lead to a significant release of 5HT from platelets. However, the increased urinary excretion of HIAA in patients with pulmonary hypertension indicates an increased turnover of 5HT, probably due to an increased number of intrapulmonary neuroepithelial cells or a higher metabolic rate of 5HT within those cells.