In 23 patients with moderate to severe Huntington's disease (HD) and 21 normal volunteers, the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in the cerebellum, thalamus, striatum, and cortex using positron emission tomography and the ¹⁸F-deoxyglucose method. In contrast to previous reports, rCMRGlc was reduced not only in the striatum, but also in the cerebral cortex of patients with HD as compared with normal subjects. No significant difference between HD patients and normal subjects was found for thalamic and cerebellar rCMRGlc. To investigate the relationship between the clinical status and rCMRGlc, correlation coefficients for the clinical data were calculated for absolute values of rCMRGlc and for cerebellar ratios (CR) of rCMRGlc. The duration of chorea correlated significantly only with the absolute values of frontoparietal and temporo-occipital rCMRGlc and with the CRs of most cortical regions evaluated. The severity of chorea correlated significantly only with lentiform nucleus rCMRGlc. The severity of dementia correlated significantly only with the frontoparietal and temporo-occipital rCMRGlc, the CRs of most cortical regions, and the CR for the caudate nucleus. The degree of disability correlated significantly with the CRs of all regions evaluated except the occipital and the superior frontal cortex. It appears from this study that there is a reduction not only for the striatum but also for cortical rCMRGlc in patients with manifest HD, and that the cortical reduction of rCMRGlc contributes to the severity of clinical symptoms in these patients. This challenges the concept that dementia in HD is of purely subcortical origin.