The comparative prevalence of leukoencephalopathic changes in 119 young and old inpatients and outpatients with major depression was examined. Patients underwent magnetic resonance imaging (MRI) examinations with T1- and T2-weighted pulse sequences. Leukoencephalopathic changes were uncommon in depressed patients and medical control subjects younger than 45 years of age. Such changes were, however, seen in approximately 44% of older depressed patients and 30% of elderly medical control subjects.