The effect of vasoactive stimuli on cerebral blood flow (CBF) has been variously reported as normal or impaired by hypoglycemia. We measured regional CBF (rCBF) in contralateral somato-sensory cortex at rest and during vibrotactile stimulation of one hand in four normal awake human volunteers during fasting euglycemia (5.1-5.2 mumol/ml) with 0.9% saline infusion, euglycemia (5.1-5.2 mumol/ml) with hyperinsulinemic clamp, mild hypoglycemia (3.2-3.6 mumol/ml) with hyperinsulinemic clamp, and moderate hypoglycemia (2.3-3.2 mumol/ml) with hyperinsulinemic clamp. No changes in mean arterial pressure, arterial PCO2, or arterial oxygen content occurred. There was no change in the magnitude of the normalized rCBF response to physiological brain stimulation with progressive arterial hypoglycemia (r = 0.10, P = 0.73). We interpret this to mean that there was a progressive reduction in cerebral glucose delivery to the area of physiological activation as arterial glucose concentrations fell. Therefore, the increase in rCBF during physiological brain activation is not regulated by a mechanism that matches local cerebral glucose supply to local cerebral glucose demand.