To clarify the developmental brain changes during adolescence, brain morphology was compared between healthy younger adolescent and elder adolescent subjects using both voxel-based morphometry (VBM) and volumetric region-of-interest (ROI) analysis of magnetic resonance imaging (MRI). High-resolution three-dimensional MRI scans were acquired in 23 (10 males and 13 females) younger adolescent subjects (13-14 years) and 30 (15 males and 15 females) elder adolescent subjects (19-21 years). Whole-brain analysis by VBM revealed that the elder adolescent subjects had significantly more gray matter in the left medial temporal regions than the younger adolescent subjects and significantly less gray matter in the left medial frontal region (Brodmann area 6). In the volumetric analysis, significantly less cerebral gray matter volume and significantly greater cerebral white matter volume were found in elder adolescents compared with younger adolescents. The volume of the hippocampus was significantly larger in male elder adolescents than in male younger adolescents. The volume of the parahippocampal gyrus did not differ between younger and elder adolescent subjects. These results suggest a robust maturational process ongoing in the human hippocampus during adolescence, especially in males. The possible relevance of these findings to progress in myelination and implications in psychiatric disorders were discussed.