BACKGROUND The devastating effects of hypotension on head-trauma-related mortality are well known. This study evaluates the systemic and cerebral hemodynamic responses to volume replacement with 3% hypertonic saline (HSS) or lactated Ringer's solution (LR), during the acute phase of hemorrhagic shock (HS) associated with traumatic brain injury (TBI). METHODS Fifteen dogs were assigned to one of three groups (n = 5, each) according to the volume replacement protocol, infused after TBI (brain fluid percussion, 4 atm) and epidural balloon to an intracranial pressure (ICP) higher than 20 mm Hg and HS, induced by blood removal to a mean arterial pressure (MAP) of 40 mm Hg in 5 minutes: Group HS+TBI+HSS (8 mL/kg of 3% HSS), HS+TBI+LR (16 mL/kg LR), and Group HS+TBI (controls, no fluids). We simulated treatment during prehospital and early hospital admission. Groups HS+ TBI and HS+TBI+LR received shed blood infusion to a target hematocrit of 30%. Measurements included shed blood volume, fluid volume infused to restore MAP, MAP, cardiac output, cerebral perfusion pressure, cerebral and systemic lactate, and oxygen extraction ratios. RESULTS Fluid replacement with HSS 3% or LR promoted major hemodynamic benefits over control animals without luids. Cerebral perfusion pressure was higher than controls and similar between treated groups; however, HSS 3% infusion was associated with lower ICP during the "early hospital phase" and a higher serum sodium and osmolarity. CONCLUSIONS In the event of severe head trauma and hemorrhagic shock, the use of HSS 3% and larger volumes of LR promote similar systemic and cerebral hemodynamic benefits. However, a lower ICP was observed after HSS 3% than after LR.