BACKGROUND AND PURPOSE: Increased frequency and severity of signal hyperintensities have been regularly reported in elderly depressed patients compared with normal subjects, however, greater neuroanatomic localization of lesions has been limited. METHODS: T2-weighted MRI scans in elderly depressed patients (n = 35) and normal comparison subjects (n = 31) were assessed for signal hyperintensities in lateralized discrete brain regions. RESULTS: Logistic regression revealed that left frontal deep white matter (P<.005) and left putaminal (P<.04) hyperintensities significantly predicted depressive group assignment. CONCLUSIONS: Findings suggest that greater neuroanatomic localization of hyperintensities than heretofore appreciated may relate to late-life depression.