This study is the first report on the effects of total sleep deprivation (about 32 h) on regional cerebral glucose metabolism during wakefulness in man, using positron emission tomography (PET) with F-18 deoxyglucose (FDG). Sleep deprivation leads to a significant reorganization of regional cerebral metabolic activity, with relative decreases in the temporal lobes and increases in visual cortex. Absolute glucose metabolic measurements indicate a decrease in thalamus, basal ganglia, white matter, and cerebellum. No overall decrease in whole brain metabolism was noted after sleep deprivation. As expected, sleep deprivation significantly reduced visual vigilance as assessed by the continuous performance test and this decrease was correlated significantly with reduced metabolic rate in thalamic, basal ganglia, and limbic regions.