The authors conducted a 6-year follow-up of 16 patients with late-life depression to evaluate the relationships between clinical and neuroradiologic variables and disease outcome. Patients had a comprehensive neuropsychiatric evaluation and magnetic resonance imaging (MRI) at baseline and follow-up. Eight of the 16 developed a chronic course of unremitting major depression sufficient to cause significant psychosocial impairment. Six patients with a chronic course and four patients with a non-chronic course of depression had white matter hyperintensities (WMH) on MRI at baseline. Four patients whose WMH increased in size over time developed a chronic unremitting course of depression. No patients with non-chronic depression had large areas of WMH at baseline or exhibited increased WMH size over time. Chronic depression was associated with severity of cerebrovascular risk factors, apathy, and poor quality of life. Treatment and prevention of cerebrovascular disease may improve the outcome of late-life depression.