Rates of cerebral blood flow (CBF) and glucose consumption (CMR(glc)) rise in cerebral cortex during continuous stimulation, while the oxygen-glucose index (OGI) declines as an index of mismatched coupling of oxygen consumption (cerebral metabolic rate of oxygen-CMRO(2)) to CBF and CMR(glc). To test whether the mismatch reflects a specific role of aerobic glycolysis during functional brain activation, we determined CBF and CMRO(2) with positron emission tomography (PET) when 12 healthy volunteers executed finger-to-thumb apposition of the right hand. Movements began 1, 10, or 20 minutes before administration of the radiotracers. In primary and supplementary motor cortices and cerebellum, CBF had increased at 1 minute of exercise and remained elevated for the duration of the 20-minute session. In contrast, the CMRO(2) numerically had increased insignificantly in left M1 and supplementary motor area at 1 minute, but had declined significantly at 10 minutes, returning to baseline at 20 minutes. As measures of CMR(glc) are impossible during short-term activations, we used measurements of CBF as indices of CMR(glc). The decline of CMRO(2) at 10 minutes paralleled a calculated decrease of OGI at this time. The implied generation of lactate in the tissue suggested an important hypothetical role of the metabolite as regulator of CBF during activation.