The aims of this study were to find brain regions in which gray matter volume was reduced and to show the capability of voxel-based morphometry (VBM) analysis for lateralizing epileptogenic zones in medial temporal lobe epilepsy (mTLE). The findings were compared with fluorodeoxyglucose positron emission tomography (FDG PET). Materials and Methods: MR T1-weighted images of 12 left mTLE and 11 right mTLE patients were compared with those of 37 normal controls. Images were transformed to standard MNI space and averaged in order to create study-specific brain template. Each image was normalized to this local template and brain tissues were segmented. Modulation VBM analysis was performed in order to observe gray matter volume change. Gray matter was smoothed with a Gaussian kernel. After these preprocessing, statistical analysis was performed using statistical parametric mapping software (SPM99). FDG PET images were compared with those of 22 normal controls using SPM. Results: Gray matter volume was significantly reduced in the left amygdala and hippocampus in left mTLE. In addition, volume of cerebellum, anterior cingulate, and fusiform gyrus in both sides and left insula was reduced. In right mTLE, volume was reduced significantly in right hippocampus. In contrast, FDG uptake was decreased in broad areas of left or right temporal lobes in left TLE and right TLE, respectively. Conclusions: Gray matter loss was found in the ipsilateral hippocampus by modulation VBM analysis in medial temporal lobe epilepsy. This VBM analysis might be useful in lateralizing the epileptogenic zones in medial temporal lobe epilepsy, while SPM analysis of FDG PET disclosed hypometabolic epileptogenic zones.