Frontotemporal dementia (FTD) is a common cause of presenile dementia. The aim of the current study was 2-fold: (a) to delineate the brain regions with reduction of glucose metabolism, and (b) to investigate the hemispheric asymmetry of glucose metabolism in FTD using F-18-FDG PET. Methods: We compared the regional metabolic patterns on F-18-FDG PET images obtained from 29 patients with FTD and 11 healthy subjects using a voxel-wise analysis (statistical parametric mapping [SPM]). The hemispheric asymmetry of glucose metabolism was computed based on 2 different measures: one (Al-ROI) by counting the F-18-FDG activity of each hemisphere on the normalized and spatially smoothed PET images and the other (Al-SPM) by counting the number of voxels with significant hypometabolism based on SPM results. Results: Significant hypometabolism was identified in extensive prefrontal areas, cingulate gyri, anterior temporal regions, and the left inferior parietal lobule. Hypometabolism was also found in the bilateral insula and uncus, left putamen and globus pallidus, and medial thalamic structures. Frontal hypometabolism was more prominent in the left hemisphere than in the right. Twenty-six (90%) of the 29 patients with FTD had Al-ROI values indicating significant lateralization of glucose metabolism; 18 patients had hypometabolism more severe on the left than right side, and only 8 patients had the opposite pattern. Results from Al-SPM showed similar patterns. Conclusion: The voxel-wise analysis of F-18-FDG PET images of patients with FTD revealed hypometabolism in extensive cortical regions, such as frontal and anterior temporal areas, cingulate gyri, uncus, and insula and subcortical areas, including basal ganglia (putamen and globus pallidus) and medial thalamic regions. The hemispheric asymmetry of hypometabolism (more frequently lateralized to the left) was common in patients with FTD, which may be another metabolic feature that helps to differentiate FTD from Alzheimer's disease or other causes of dementia.