Studies have shown that active hepatocellular function is depressed early after trauma-hemorrhage and persists despite resuscitation with two or three times (x) the volume of maximum bleedout (MB) with lactated Ringer’s solution (LR). However, it is not known if a larger volume of fluid resuscitation corrects this dysfunction. To study this, rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the MB volume was returned in the form of LR, and then resuscitated with 4x or 5x the volume of MB with LR. Three doses of indocyanine green (ICG) were given intravenously and [ICG] measured in vivo using an in-vivo hemoreflectometer. The initial velocity of the clearance of ICG was calculated. Maximal velocity of the clearance (Vmax: the number of functional ICG receptors) and kinetic constant (Km: the efficiency of the active transport) were determined from the Lineweaver-Burk plot. Vmax decreased during hemorrhage, was restored to control levels at 0-4 hours after resuscitation, but decreased at 4-8 hours after resuscitation despite restoration of cardiac output following resuscitation with 5x LR. This could be the result of increased TNF release. The Km also decreased during hemorrhage, but increased at 0-1.5 hours and remained at control levels even 4-8 hours after resuscitation. Thus the failure of Vmax to remain at control levels following adequate fluid resuscitation may form the basis of cellular dysfunction and multiple organ failure after severe hemorrhagic shock. © 1991 by The Williams & Wilkins Co.