SummaryAlthough the hippocampus has been found to be smaller in people with depression, the clinical relevance of this is unclear. We investigated hippocampal volume (using high-resolution magnetic resonance imaging) and 2-year outcome in 57 patients with major depression. The left and right hippocampal volumes of patients with a depression relapse were significantly smaller than those of healthy controls. Our results support the hypothesis that the hippocampus is crucial in the outcome of depression.