To investigate the role of the autonomic nervous system in cerebral blood flow (CBF) and metabolism, CBF and oxygen metabolism in patients with multiple system atrophy of the Shy-Drager syndrome type were examined. Seven patients with Shy-Drager syndrome were imaged using positron emission tomography and 15O-labeled gases. There was excellent local coupling between CBF and the cerebral metabolic rate of oxygen in the resting state. Elevation of blood pressure induced by leg raising increased CBF. The inhalation of CO2 also increased CBF in the Shy-Drager patients. These results showed that autoregulation is impaired in Shy-Drager syndrome, but local metabolic-flow coupling in the resting state and the CBF response to CO2 inhalation are spared. We conclude that the autonomic nervous system plays an important role in autoregulation, but not in local metabolic-flow coupling in the resting state. We suggest that metabolic mechanisms may mediate resting metabolic-flow coupling.