The liver is a major organ involved in multiple organ failure (MOF) following hemorrhage and trauma. However, it is not known if active hepatocellular membrane transport, measured by in vivo indocyanine green (ICG) clearance, is depressed after hemorrhage and if it persists after resuscitation. To study this, rats were bled to and maintained at a mean BP of 40 mm Hg until 40% of maximum bleedout (MB) volume was returned in the form of Ringer's lactate (RL). The rats were then resuscitated with 2× or 3× the volume of MB with RL and hepatocellular function was determined at various intervals. ICG, two to four doses (0.167-1.667 mg/kg BW), was given intravenously and [ICG] was continuously recorded without the need of blood sampling, using an in vivo hemoreflectometer with computer-assisted data acquisition. Initial velocity of clearance (V0) was calculated from [ICG]vs time (t) according to [ICG] = e∧ (a + bt + ct∧ 2), where eab is V0. Maximal velocity of clearance (Vmax and Km, a kinetic constant representing the efficiency of the active transport process, were determined from the Lineweaver-Burk plot. The results indicate that Vmax decreased by 66% at MB and remained depressed despite fluid resuscitation. Km decreased by 58% at MB, returned to prehemorrhage level after 3× RL but was not maintained and it decreased by 60% at 4 hr after resuscitation. This in vivo study demonstrates that active hepatocellular function is significantly depressed early after hemorrhage and persists despite resuscitation with RL and may form the basis of the MOF observed after severe and prolonged hemorrhage. © 1990.