Splanchnic and renal extraction of hyaluronan was determined in patients with alcoholic cirrhosis (n = 9), non-cirrhotic alcoholic liver disease (n = 5), and controls without liver disease (n = 19) in the supine fasting condition. Arterial plasma concentration of hyaluronan was significantly increased in patients with cirrhosis (mean 480 micrograms/l) as compared to non-cirrhotic patients (29 micrograms/l, P less than 0.001) and controls (25 micrograms/l, P less than 0.001), whereas no difference was present between the two last-mentioned groups. In patients with liver disease, circulating hyaluronan was inversely correlated to indocyanine green clearance (r = -0.85, P less than 0.001) and to galactose elimination capacity (r = -0.62, P less than 0.02), but positively correlated to portal pressure (determined as wedged-to-free hepatic vein pressure) (r = 0.92, P less than 0.001). Splanchnic extraction ratio (arterio-hepatic venous extraction ratio) had a mean value of 0.14 in patients with cirrhosis as compared to 0.36 in non-cirrhotic patients (P less than 0.05) and 0.34 in controls (P less than 0.025). Splanchnic hyaluronan extraction was not correlated to liver function tests or portal pressure. In patients with alcoholic liver disease no significant renal hyaluronan extraction was found as compared to an extraction ratio of 0.17 in controls (P less than 0.05). Our results suggest that the increased level of circulating endogenous hyaluronan found in patients with cirrhosis is caused by a combination of increased supply to and decreased extraction from plasma.