Plasma catecholamines may play a role in the pathogenesis of pulmonary hypertension in congenital heart disease with increased pulmonary blood flow. At cardiac catheterization, blood samples were obtained before and after passage of the lung in patients with congenital heart disease with normal pulmonary blood flow (n=39), elevated pulmonary blood flow with normal pulmonary pressure and normal pulmonary vascular resistance (PVR) in patients with atrial septal defect (ASD) (n=57) or ventricular septal defect (VSD) (n=12), and increased pulmonary blood flow, pressure and vascular resistance in patients with ASD, VSD or both (n=22), or in patients with primary pulmonary hypertension (n=4). Plasma catecholamines were determined by reversed phase high performance liquid chromatography and electrochemical detection (HPLC-ECD). In patients with elevated PVR elevated norepinephrine levels (NE) were observed. In contrast, epinephrine levels (E) were not associated with the development of pulmonary hypertension. Patients with primary pulmonary hypertension had the highest levels of NE while patients with associated Down's syndrome had significantly lower epinephrine levels. Pulmonary plasma norepinephrine levels are increased in patients with elevated pulmonary vascular resistance. Whether this phenomena is the cause or sequalae of pulmonary hypertension needs further examination. In the future, plasma catecholamines may serve as a diagnostic feature or may result in further therapeutic options.