Volume expansion associated with brain infarction occurs in perfusion-diffusion mismatch of magnetic resonance imaging. We aimed at elucidating the metabolic impairment of this phenomenon with (15)O positron emission tomography and perfusion and diffusion magnetic resonance imaging. Eleven patients with acute unilateral embolic occlusion of the internal carotid or middle cerebral artery were studied within 6 hours of onset. Regional cerebral blood flow and cerebral metabolic rate of oxygen (CMRO(2)) were compared with those in the contralateral cerebral hemisphere. The relative apparent diffusion coefficient of water was estimated as a marker of cytotoxic edema. Relative cerebral blood flow and relative CMRO(2) in an evolving infarct (normal diffusion initially, but abnormal on day 3) were significantly (p < 0.05) less than those in the periinfarct area (normal diffusion initially and on day 3). The relative apparent diffusion coefficient between the evolving infarct and periinfarct showed no significant difference. These findings indicated that the initial 3-day volume expansion of an embolic brain infarction was associated with disturbed CMRD(2) but not with cytotoxic edema as early as 6 hours after onset. The "metabolic penumbra" defined as normal water diffusion with depressed CMRO(2) is a target to reduce the volume expansion of brain infarction.