This study examined the densitometric and topographic detail of high resolution 3D digital postmortem cryosectioned brain images. Anatomic image data and histology from cryosectioned human brain were compared to in vivo MRI for the ability to delineate neuroanatomic structure. 3D surface reconstructions in the Talairach and Tournoux atlas ("Co-planar stereotaxic atlas of the human brain", Thieme, New York, 1988) coordinate system enabled morphometric comparisons for a representative sample of neuroanatomic structures. Spatial resolution of cryosection images averaged 200 and 170 microns/pixel for whole head and brain, respectively, and 40 microns/pixel for isolated the brain regions. Anatomic detail was far superior to MRI, particularly in deep subcortical regions such as the basal ganglia and in mesencephalic nuclei and tracts. Digital repositioning in the Talairach coordinate system enabled efficient structure localization and morphometric comparison. Histology from collected tissue sections provided cytologic detail that could be mapped to its approximate 3D context. This approach permits comprehensive morphometric analyses necessary for an anatomic framework to a digital atlas of the human brain.