The effect of pentobarbital and isoflurane on cerebral glucose metabolism (CMRglc) was studied in thermally injured rat brain using quantitative autoradiography. In awake lesioned animals, CMRglc in cortical regions ipsilateral to the injury was reduced to 50% of normal while little if any decrease was observed in contralateral cortical regions and subcortical regions bilaterally. Treatment of lesioned animals with pentobarbital or isoflurane further reduced CMRglc, but more in the hemisphere contralateral to the injury than on the injured side. Thus, the side-to-side difference in cortical CMRglc present in the awake lesioned animals was abolished by the anesthetics. The results support the hypothesis that CMRglc depression associated with a focal cold injury is functional in nature. Reduction of metabolism by anesthetics in functionally depressed brain is limited by the decrease in CMRglc associated with the injury.