The magnitude of hepatic plasma flow in patients with liver failure and hepatic encephalopathy (HE) is unknown because a reliable flow estimate has not been available. The purpose of this study was to estimate hepatic plasma flow in patients with HE and to evaluate indocyanine green (ICG) and sorbitol as test compounds. Fourteen patients with acute liver failure (ALF) and nine patients with chronic liver failure (CLF), all with HE grade II or more, were studied. After hepatic vein catheterization, hepatic plasma flow was estimated by use of constant infusion, simultaneous arterial and hepatic vein concentration measurements, and calculated according to Fick's principle. The hepatic extraction fraction of d-sorbitol 0.179 ± 0.144 (mean ± SD) was higher than the hepatic extraction fraction of ICG 0.054 ± 0.085 (P < .001). The low hepatic extraction fraction of ICG rendered this compound unfit for estimation of hepatic plasma flow in these patients. In contrast, by using d-sorbitol the hepatic plasma flow could be estimated in 21 of 23 patients with a median SD of 8.4% (range, 2.6% to 29%). The d-sorbitol estimated hepatic plasma flow was 1.2 ± 0.5 L/min (n = 12) in patients with ALF and 1.4 ± 0.9 L/min (n = 9) in patients with CLF. These values are higher than what has been reported in normal subjects and in patients with cirrhosis without HE. An elevated hepatic flow should increase oxygen delivery and may enhance the failing liver's ability to remove substances from the blood. At the same time, hepatic first pass metabolism is reduced. We conclude that an elevated hepatic flow in these patients is of clinical importance.