Objective: It has been hypothesized that adequate concentrations of vitamin B12 and folate are essential to maintain the integrity of the neurological systems involved in mood regulation, but epidemiologic evidence for such a link in the general population is unavailable. This study examined whether community-dwelling older women with metabolically significant vitamin B12 or folate deficiency are particularly prone to depression. Method: Serum levels of vitamin B12, folate, methylmalonic acid, and total homocysteine were assayed in 700 disabled, nondemented women aged 65 years and over living in the community. Depressive symptoms were measured by means of the Geriatric Depression Scale and categorized as no depression, mild depression, and severe depression. Results: Serum homocysteine levels, serum folate levels, and the prevalences of folate deficiency and anemia were not associated with depression status. The depressed subjects, especially those with severe depression, had a significantly higher serum methylmalonic acid level and a nonsignificantly lower serum vitamin B12 level than the nondepressed subjects. Metabolically significant vitamin B12 deficiency was present in 14.9% of the 478 nondepressed subjects, 17.0% of the 100 mildly depressed subjects, and 27.0% of the 122 severely depressed women. After adjustment for sociodemographic characteristics and health status, the subjects with vitamin B12 deficiency were 2.05 times as likely to be severely depressed as were nondeficient subjects. Conclusions: In community- dwelling older women, metabolically significant vitamin B12 deficiency is associated with a twofold risk of severe depression.