Although sleep deprivation interferes with biological processes essential for performance, health, and longevity, previous studies have failed to reveal any structural or functional changes in brain. We have therefore measured local rates of cerebral glucose utilization (ICMRglc) with the quantitative autoradiographic 2–14C-deoxyglucose method in an effort to determine if and, if so, where sleep deprivation might affect function in sleep-deprived rats. Sleep deprivation was maintained for 11–12 d, long enough to increase whole body energy metabolism, thus confirming that pathophysiological processes that might involve brain functions were evolving. Deep brain temperature was also measured in similarly treated rats and found to be mildly elevated relative to core body temperature. Despite the increased deep brain temperature, systemic hypermetabolism, and sympathetic activation, ICMRglc was not elevated in any of the 60 brain structures examined. Average glucose utilization in the brain as a whole was unchanged in the sleep-deprived rats, but regional decreases were found. The most marked decreases in ICMRglc were in regions of the hypothalamus, thalamus, and limbic system. Mesencephalic and pontine regions were relatively unaffected except for the central gray area. The medulla was entirely normal. The effects of sleep deprivation on brain tended, therefore, to be unidirectional toward decreased energy metabolism, primarily in regions associated with mechanisms of thermoregulation, endocrine regulation, and sleep. Correspondence was found between the hypometabolic brain regions and some aspects of peripheral symptoms.