The effects on food intake, blood glucose and the binding of guanosine 5-diphosphate (GDP) to mitochondria from interscapular brown adipose tissue (IBAT) were examined following the injection of 2-deoxy-D-glucose (2-DOG) into the third ventricle of the brain. Microinjections of 2-DOG increased food intake and blood glucose within 30 to 60 min, but binding of GDP to mitochondria from IBAT, on the other hand, was reduced. The order of sensitivity to 2-DOG was IBAT--feeding--hyperglycemia. Implantation of a 50 mg pellet of corticosterone inhibited the stimulatory effect of 2-DOG on feeding and hyperglycemia and prevented the inhibition of GDP binding to mitochondria from IBAT. These data are consistent with the hypothesis that glucocorticoid may inhibit glucose metabolism at multiple sites in the hypothalamus.