Regional cerebral glucose metabolism was studied in nine patients with progressive supranuclear palsy (PSP). (18F)-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) revealed general cerebral hypometabolism in all PSP patients in comparison with an age-matched reference group. When comparing the degree of regional metabolic deterioration, a consistent pattern of the most affected brain regions became obvious: the strongest significant alteration of cerebral glucose metabolism was observed in subcortical regions, e.g. in caudate nucleus, lentiform nucleus and upper mid-brain, which showed nerve cell loss in previous pathological studies. Less severe, but still significant hypometabolism was observed in frontal cortex. This pattern of hypometabolism was distinctly different from that typically seen in dementias of Alzheimer's type. The present data show that PET findings agree with histopathological studies: PSP is a primarily subcortical disease with secondary inactivation of cortical, especially of frontal brain regions.