White matter hyperintensities (WMHs) are a common finding in normal elderly persons. We studied the biological damage associated with WMHs by assessing the correspondence between WMH location and regional gray matter loss.Voxel-based morphometry of the gray matter was carried out with statistical parametric mapping on high resolution MR images.Neurologically intact persons with mainly anterior (frontal>parieto-occipital; N = 39) and mainly posterior WMHs (parieto- occipital>frontal; N = 14) were compared with a group devoid of WMHs (N = 80). Subjects with mainly frontal WMHs had bilateral frontal (medial, superior, and inferior gyri) atrophy in gray matter, while subjects with mainly posterior WMHs had more diffuse atrophy, involving mainly the frontal but also the right insular region. Our findings suggest that frontal WMHs are associated with frontal gray matter damage while parietooccipital WMHs seem to have a weaker and more diffuse impact on gray matter.