To examine the effect of liver transplantation on the respiratory and cardiovascular functions, ventilation/perfusion relationships were determined by multiple inert gas elimination technique in six patients with end-stage liver disease 1 to 19 mo before and 2 to 6 mo after liver transplantation. Cardiac output and pulmonary vascular pressures were measured after catheterization of the pulmonary artery. All patients had normal spirometry and chest x-ray films before transplantation. PaO2 before transplantation was 78.8 +/- 7.4 mm Hg (range = 51.8 to 102.8 mm Hg). All patients had perfusion of poorly ventilated lung regions (low ventilation/perfusion relationships) varying from 3% to 19% of cardiac output (mean = 8.5% +/- 2.4% of cardiac output) and two patients had intrapulmonary shunting (3% and 20% of cardiac output). Measured and calculated PaO2 agreed closely, indicating absence of pulmonary diffusion abnormality, as well as of extrapulmonary shunting. After transplantation, PaO2 normalized in all patients, and both shunting and low ventilation/perfusion relationships disappeared. Cardiac output decreased from 9.1 +/- 1.4 to 6.6 +/- 0.5 L/min (p less than 0.05), and the pulmonary vascular resistance increased from 0.69 +/- 0.14 to 1.64 +/- 0.43 mm Hg/L/min (p less than 0.05). The systemic vascular resistance also increased (before = 8.7 +/- 1.0; after = 15.3 +/- 1.1 mm Hg/L/min; p less than 0.001). Normalization of respiratory and cardiovascular alterations, after liver transplantation, in patients with end-stage liver disease indicates that these changes have a direct functional relationship to the diseased liver. It is hypothesized that this is part of a "hepatopulmonary syndrome,' which in similarity to the hepatorenal syndrome disappears with improved liver function.