This paper studies brain morphometry variation associated with XXY males (Klinefelter's syndrome) by using an automated whole-brain volumetric analysis method. The application to 34 XXY males and 62 normal male controls reveals pronounced volume reduction in the brains of XXY males, relative to the brains of normal controls, localized at the insula, temporal gyri, amygdala, hippocampus, cingulate, and occipital gyri. Most of these statistically significant regions are in the gray matter structures, with the exception of one cluster of atrophy involved in white matter structure, i.e., right parietal lobe white matter. Compared to previous findings documented in the literature, our findings provide a better spatial localization of the affected regions. In addition to the reduction of local volume, overall enlargement of ventricles and overall volume reduction of both white matter and gray matter are also found in XXY males.