Using brain magnetic resonance imaging (MRI) and high-resolution computed tomography (CT), we identified changes in the subcortical white matter in 44 of 67 elderly depressed inpatients (66%) referred for electroconvulsive therapy (ECT). This "leukoencephalopathy" was frequently associated with other structural brain changes, including cortical atrophy, lateral ventricular enlargement, and lacunar infarctions of the basal ganglia and thalamus. Many (58%) of the patients had developed late-onset depressive disorders, and the majority (86%) had been refractory to and/or intolerant of antidepressant drug therapy. Nevertheless, all but 1 of the 44 patients subsequently responded to a course of ECT, which in general was well tolerated. Although the precise etiology of the leukoencephalopathy remains unclear, clinical data suggest that it may result from arteriosclerotic disease of the medullary arteries that supply the subcortical brain regions. Several lines of evidence suggest that leukoencephalopathy may have implications for the pathophysiology of depressive illness, at least in some elderly patients.