Three weeks of hypoxic exposure results in a spectrum of systemic physiological and local brain tissue adaptations. Cytochrome oxidase histochemistry was used as an indicator of changes in energy demand in response to hypoxia. We found overall cytochrome oxidase activity decreased in hypoxic adapted rats as compared to normoxic control rats. Some regions, notably layer 3 of the frontal cerebral cortex, layer 4 of the parietal sensory barrel fields, lacunosum moleculare hippocampi, and specific nuclei of the rostral ventral medulla, though exhibiting cytochrome oxidase activity decreases of 16-27%, still retain their relatively higher levels of activity. We conclude that there is a hypometabolic component of the rat brain adaptation to continued hypoxia.