The regional cerebral metabolic effects of 30 min of exposure to 0.5, 1.0, 1.5, and 2.0% carbon monoxide (CO) were studied in lightly anesthetized rats by measurement of energy phosphates and glycolytic - citric acid cycle substrates in the basal ganglia, hippocampus-thalamus, and cerebellum. In all three regions 0.5 and 1.0% CO gave rise to increases in tissue lactate, but since ATP and the energy charge of the adenylate pool (ECP) remained unchanged from control, it is concluded that energy state was unaltered at these levels of CO. At 1.5% CO the basal ganglia region showed decreases in ATP and ECP, whereas these values for cerebellum and hippocampus=thalamus were unchanged from control. At 2.0% CO all areas showed decreases in APT and ECP and increases in ADP and AMP. The patterns of change in glycolytic and citric acid cycle substrates were similar in all three areas. The results indicated that the energy homeostasis of the basal ganglia is less well maintained in this form of experimental hypoxia.