Objectives of the study was to investigate regional gray matter changes in the first-episode schizophrenia patients. We used optimized voxel-based morphometry in 22 first-episode schizophrenia patients and 18 healthy controls of comparable age, gender and handedness. The first episode group had significantly reduced gray matter volume in the prefrontal cortex (inferior and middle prefrontal gyrus, cingulate gyrus). We identified no differences in temporal cortex. Our data support the theoretical assumption that prefrontal dysfunction underlines the primary pathology and clinical manifestation of schizophrenia. We are inclined to explain the differences in the pattern of morphological changes reported in other first-episode studies - especially the lack of changes in the temporal cortex - by heterogenity of schizophrenia, potential progression and antipsychotic medication effect.