Fourteen patients who developed a psychotic depression after age 45 were compared with 72 non-psychiatrically ill elderly control subjects using neuroimaging and neuropsychological (NP) tests. Despite the fact that the patients were not studied if they had an obvious dementia or neurological disease, structural brain abnormalities were found in approximately two-thirds of patients and in less than 10% of controls. The most common abnormality, subcortical white matter (WM) lesions, was thought to be vascular in etiology. Also, tumor and primary degenerative dementia were found more frequently in the patients. Compared to an age-, sex-, and education-matched control group, the patients performed more poorly on NP tests of frontal lobe, memory, and visual spatial abilities. Diagnostic evaluation of the patient with late-onset psychotic depression should include computed tomography or magnetic resonance imaging as structural brain abnormalities are common in these patients.