Activation-induced increase in cerebral blood flow is coupled to enhanced metabolic activity, maybe with brain tissue redox state and oxygen tension as key modulators. To evaluate this hypothesis at the onset of exercise in humans, blood was sampled at 0.1 to 0.2 Hz from the radial artery and right internal jugular vein, while middle cerebral artery mean flow velocity (MCA V(mean)) was recorded. Both the arterial and venous lactate-to-pyruvate ratio increased after 10 s (P < 0.05), and the arterial ratio remained slightly higher than the venous (P < 0.05). The calculated average cerebral capillary oxygen tension decreased by 2.7 mmHg after 5 s (P < 0.05), while MCA V(mean) increased only after 30 s. Furthermore, there was an unaccounted cerebral carbohydrate uptake relative to the uptake of oxygen that became significant 50 s after the onset of exercise. These findings support brain tissue redox state and oxygenation as potential modulators of an increase in cerebral blood flow at the onset of exercise.