This study examined regional structural changes in the whole brain in 45 medicated patients with schizophrenia (23 males and 22 females), comparing with 42 age- and sex-matched healthy volunteers (22 males and 20 females). Automated voxel-based analysis on three-dimensional magnetic resonance imaging (MRI) was conducted using statistical parametric mapping (SPM). Compared with the controls, relative gray matter in the patients was significantly reduced in the left superior temporal, left middle and inferior frontal, right inferior frontal, and bilateral anterior cingulate and medial temporal areas. Gray matter reductions in the left superior temporal and prefrontal areas were found predominantly in the male patients, while the anterior cingulate gray mater reduction was more striking in the female patients. On the contrary, significant gray matter increases in the patients were found in the parietal areas and the cerebellum. In the white matter, significant reduction was found in the bilateral anterior limbs of the internal capsule and the superior occipitofrontal fasciculus, whereas the bilateral parietal white matter showed significant increases. These results suggest that a pathological process in schizophrenia predominantly affects the fronto-temporolimbic-paralimbic regions. Reduced white matter in the connecting bundles, which was first found in this study, may imply morphological substrates for abnormalities in the fronto-thalamic and fronto-temporolimbic connectivity in schizophrenia.