In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of fluid resuscitation versus arginine vasopressin (AVP) combined with hypertonic-hyperoncotic hydroxyethyl starch solution (HHS) on cerebral perfusion pressure (CPP) and on cerebral metabolism using intracerebral microdialysis. Sixteen anesthetized pigs were subjected to uncontrolled liver bleeding until hemodynamic decompensation, followed by resuscitation using either fluid (n = 8) or AVP/HHS (n = 8). Thirty minutes after drug administration, bleeding was controlled by manual compression, and colloid and crystalloid solutions were administered in both groups. All surviving animals were observed for one hour. After hemodynamic decompensation, fluid resuscitation resulted in a smaller increase of CPP than did AVP/HHS (mean +/- sem; 24 +/- 5 vs 45 +/- 7 mm Hg; P < 0.01). Mean (+/- sem) cerebral venous partial pressure of oxygen was significantly decreased (P < 0.01) 5 min after fluid compared with 5 min after AVP/HHS administration (36 +/- 3 vs 64 +/- 4 torr). Cerebral metabolism was comparable in both groups. In conclusion, AVP/HHS proved to be superior to fluid in the initial phase of therapy with respect to CPP and cerebral oxygenation, but was comparable to fluid regarding cerebral metabolism and secondary cell damage in surviving animals.