Background Although the effects of propofol on cerebral metabolism have been studied in animals, these effects have yet to be directly examined in humans. Consequently, we used positron emission tomography (PET) to demonstrate in vivo the regional cerebral metabolic changes that occur in humans during propofol anesthesia. Methods Six volunteers each underwent two PET scans; one scan assessed awake‐baseline metabolism, and the other assessed metabolism during anesthesia with a propofol infusion titrated to the point of unresponsiveness (mean rate + SD 7.8 + 1.5 mg *symbol* kg1 *symbol* h1). Scans were obtained using the18 fluorodeoxyglucose technique. Results Awake whole‐brain glucose metabolic rates (GMR) averaged 29 + 8 micro moles *symbol* 100 g1 *symbol* min1 (mean plus/minus SD). Anesthetized whole‐brain GMR averaged 13 + 4 micro moles *symbol* 100 g1 *symbol* min1 (paired t test, P < 0.007). GMR decreased in all measured areas during anesthesia. However, the decrease in GMR was not uniform. Cortical metabolism was depressed 58%, whereas subcortical metabolism was depressed 48% (P < 0.001). Marked differences within cortical regions also occurred. In the medial and subcortical regions, the largest percent decreases occurred in the left anterior cingulate and the inferior colliculus. Conclusion Propofol produced a global metabolic depression on the human central nervous system. The metabolic pattern evident during anesthesia was reproducible and differed from that seen in the awake condition. These findings are consistent with those from previous animal studies and suggest PET may be useful for investigating the mechanisms of anesthesia in humans.