Generalized edema resulting from severe protein-losing enteropathy occurred in three patients 12, 15, and 17 months after the Fontan operation. One patient originally had tricuspid atresia and the other two, univentricular heart disease. At operation a conduit had been inserted between the right atrium and pulmonary artery. Apart from the protein loss, the patients were in good health. The cardiac catheterization data obtained 0.8 to 2.4 years (median 1.3 years) after operation in the three patients with protein-losing enteropathy were compared with those of 18 patients in whom Fontan's operation had been performed because of tricuspid atresia (eight patients) or univentricular heart disease (10 patients). All had atriopulmonary connections. The mean right and left atrial pressures and systemic blood flows measured by dye dilution in the patients with and without protein-losing enteropathy did not differ. However, the patients with protein-losing enteropathy had a higher diastolic right atrial pressure. Since maximal antegrade flow in the superior vena cava after Fontan's operation occurs during atrial diastole, these observations suggest that an increase in diastolic right atrial pressure may result in protein-losing enteropathy because of impairment of blood flow and therefore congestion in the superior vena cava, subclavian vein, and thoracic duct.