During hemorrhagic shock, increased uptake of NH3 from the gut with inadequate compensation by the liver results in hyperammonemia. The effect on brain metabolism of acute hyperammonemia alone, as compared with normocapnic hypoxia, was investigated in 11 pentobarbital anesthetized (30 mg/kg) dogs. These animals were paralyzed (pancuronium bromide) and artificially ventilated to maintain the end-tidal fraction of FETCO2) CO2 constant. Arterial blood and cerebrospinal fluid (CSF) samples were obtained following control, 30-minute hypoxia, 60-minute NH3 infusion, and 30-minute hypoxia combined with NH3 infusion. These were analyzed for PaO2, PCO2, pH, and NH3. CSF samples were further analyzed for glutamine, urea, lactate, pyruvate, and citrate. There were no significant changes in urea or citrate. Glutamine, lactate, and the lactate/pyruvate ratio were significantly elevated by hypoxia and by NH3 infusion. (formula: see text). Thus, an acute NH3 load is capable of disrupting aerobic glycolytic metabolism. Hence, hyperammonemia may affect brain function during shock.