In patients with cirrhosis, elevation of azygos blood flow has been attributed on indirect grounds to cephalad portosystemic collaterals. To gather more information on the origin of the azygos blood, we studied the oxygen and bile acid content of the azygos and mixed venous blood in patients with portal hypertension. Azygos oxygen saturation was 59.6 +/- 6.0% in 8 controls, and significantly higher in 35 patients with cirrhosis (76.7 +/- 7.6%; P less than 0.01) as well as in 6 patients with noncirrhotic portal hypertension (84.0 +/- 8.2%; P less than 0.01). High oxygen saturation, however, was not correlated to azygos blood flow in patients with cirrhosis. In cirrhotic patients, total bile acid concentrations were 28.1 +/- 20.4 mumol/l in the pulmonary artery and 25.9 +/- 17.6 mumol/l in the azygos vein, giving an azygos to mixed venous ratio of 0.95 +/- 0.18. These results provide new evidence that elevated azygos blood flow in patients with portal hypertension is derived from the portal system, and perhaps predominantly from the splenic territory.