OBJECTIVES: Depression is common in the elderly population. Although numerous neuroimaging studies have examined depressed elders, there is limited research examining how amygdala volume may be related to depression. DESIGN: A cross-sectional examination of amygdala volume comparing elders with and without a diagnosis of major depressive disorder, and between depressed subjects with early and later initial depression onset. SETTING: An academic medical center. PARTICIPANTS: Ninety-one elderly patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression (54 early-onset depressed and 37 late-onset depressed) and 31 elderly subjects without any psychiatric diagnoses. MEASUREMENTS: Amygdala and cerebral volumes were measured using reliable manual tracing methods. RESULTS: In models controlling for age, sex, and cerebral volume, there was a significant difference between diagnostic cohorts in amygdala volume bilaterally (left: F[2, 116] = 16.28, p < 0.0001; right: F[2, 116] = 16.28, p < 0.0001). Using least squares mean group analyses, both early- and late-onset depressed subjects exhibited smaller bilateral amygdala volumes than did the nondepressed cohort (all comparisons p < 0.0001), but the two depressed cohorts did not exhibit a statistically significant difference. LIMITATIONS: Limitations include missing antidepressant treatment data, recall bias, inability to establish a causal relationship between amygdala size and depression given the cross-sectional nature of the design. CONCLUSIONS: Depression in later life is associated with smaller amygdala volumes, regardless of age of initial onset of depression.