The metabolic response to brain activation in exercise might be expressed as the cerebral metabolic ratio (MR; uptake O2/glucose + 1/2 lactate). At rest, brain energy is provided by a balanced oxidation of glucose as MR is close to 6, but activation provokes a 'surplus' uptake of glucose relative to that of O2. Whereas MR remains stable during light exercise, it is reduced by 30% to 40% when exercise becomes demanding. The MR integrates metabolism in brain areas stimulated by sensory input from skeletal muscle, the mental effort to exercise and control of exercising limbs. The MR decreases during prolonged exhaustive exercise where blood lactate remains low, but when vigorous exercise raises blood lactate, the brain takes up lactate in an amount similar to that of glucose. This lactate taken up by the brain is oxidised as it does not accumulate within the brain and such pronounced brain uptake of substrate occurs independently of plasma hormones. The 'surplus' of glucose equivalents taken up by the activated brain may reach approximately 10 mmol, that is, an amount compatible with the global glycogen level. It is suggested that a low MR predicts shortage of energy that ultimately limits motor activation and reflects a biologic background for 'central fatigue'.