The authors investigated the relationships among factors of age, age at onset, and sex in depressed older adults. A group of 96 outpatients (mean age, 60) diagnosed with late-(LOD) and early-onset (EOD) major depression were assessed for severity of depression and underwent magnetic resonance imaging (MRI). The MRI scans were rated for severity of white-matter hyperintensities (WMH) and ventricle-to-brain ratio (VBR). LOD was associated with increased amounts of WMH, larger VBR, and history of hypertension. Men were more severely depressed than women, with higher rates of neurovegetative signs and history of smoking. Age correlated with increased VBR and WMH, history of hypertension, history of percipitants for the current episode, and lack of social support. Results suggest that a subgroup of men may be more at risk for LOD associated with WMH and that sex and age at onset need to be considered in future studies.