In vivo study of white matter microstructural integrity through magnetic resonance diffusion tensor imaging (DTI) permits examination of degradation of axonal circuitry that may underlie functional decline of frontally-based processes in normal adult aging. Determination of the pattern of age-related degradation of white matter microstructure requires quantitative comparison of the rostral-caudal and superior-inferior extents of the brain's white matter. To date, this has not been accomplished, probably because of significant artifacts from spatial distortion and poor signal resolution that precludes accurate analysis in prefrontal and inferior brain regions. Here, we report a profile analysis of the integrity of white matter microstructure across the supratentorium and in selected focal regions using DTI data collected at high-field strength (3 T), with isotropic voxel acquisition, and an analysis based on a concurrently-acquired field map to permit accurate quantification of artifact-prone, anterior and inferior brain regions. The groups comprised 10 younger and 10 older individuals; all were high functioning, highly educated, and in excellent health. The DTI profile analysis revealed a robust frontal distribution of low white matter anisotropy and high bulk mean diffusivity in healthy older compared with younger adults. In contrast to frontal fiber systems, posterior systems were largely preserved with age. A second analysis, based on focal samples of FA, confirmed that the age-related FA decline was restricted to frontal regions, leaving posterior and inferior brain regions relatively intact. The selective decline of anterior anisotropy with advancing age provides evidence for the potential of a microstructural white matter mechanism for the commonly observed decline in frontally-based functions.