The effect of lidocaine, 160 mg/kg, and pentobarbital, 40 mg/kg, on cerebral oxygen and glucose consumption was examined at brain temperatures of 37 degrees C, 28 degrees C, and 18 degrees C. Cerebral metabolic rate was measured in dogs on cardiopulmonary bypass circulation by using the sagittal sinus outflow technique. When studied separately, both drugs suppressed synaptic transmission and inhibited metabolism, and a maximum effect was obtained when the EEG became flat. Using halothane 1-1.5 per cent as the control condition, this function-metabolism coupled inhibition was about 30 per cent. When the drugs were studied in combination, it was found that when lidocaine was given after pentobarbital, it caused an additional metabolic inhibition of 15-20 per cent, while pentobarbital given after lidocaine had no effect. It is concluded that pentobarbital has no inhibitory effect on cerebral metabolism in the absence of synaptic activity, while lidocaine--in addition to the effect related to suppression of synaptic transmission--has a specific "membrane stabilizing" effect. In analogy to its local anesthetic action, lidocaine blocks the Na+ channels and restricts the Na+-K+ leak fluxes. The load on the ion pump is reduced and metabolism is decreased accordingly. This specific effect on lidocaine was evident also at brain temperatures of 28 degrees C and 18 degrees C. The study supports the possibility that lidocaine, like hypothermia, may provide protection for the ischemic brain.