Seventeen children with congenital heart disease undergoing elective cardiac catheterization were studied to define potential hemodynamic and echocardiographic determinants of plasma atrial natriuretic factor (ANF) concentrations. ANF concentrations in the right ventricle and femoral vein were measured by radioimmunoassay. Right ventricular levels were significantly higher than femoral venous levels (p less than 0.01), but the correlation between the 2 was high (r = 0.87, p less than 0.001). Stepwise multiple linear regression analysis demonstrated that right ventricular ANF concentrations were predicted by a combination of indexed right atrial area measured by 2-dimensional echocardiography, right atrial pressure, pulmonary resistance and heart rate (multiple r2 = 0.83). Femoral venous ANF concentrations were predicted by indexed right atrial area and systolic pulmonary artery pressure (multiple r2= 0.79). It was concluded that there are significant independent predictors of right ventricular and femoral venous plasma ANF concentrations in children with congenital heart disease. The right atrial area indexed by body surface area was the only significant predictor of both central and peripheral plasma ANF concentrations in the multivariate analysis.