The topic of vascular depression has received increasing prominence as a putative etiology of depression in later life. The authors examined one aspect of this model by comparing the burden of systemic cerebrovascular risk factors (CVRFs) in 130 psychiatric inpatients with major depression and 64 normal control (NC) subjects, all age > or = 50 years. Depressed subjects did not differ statistically from NCs on cumulative CVRF scores. Diabetes mellitus and atrial fibrillation were both associated with depression, but only atrial fibrillation retained an independent association after medical disability was statistically controlled. Among the depressed subjects, CVRF scores were not significantly associated with overall symptom severity, psychiatric disability, age at onset of depression, melancholic subtype, or psychotic depression. These data did not support the notion that a linear model of small-vessel disease might apply to the great majority of older inpatients with major depression.