A quantitative magnetic resonance imaging study of regional brain T1 spin-lattice relaxation times in 29 normal volunteers and in 20 patients with major depression revealed significantly shortened T1 relaxation times for the hippocampus in depressed patients. These differences were particularly prominent in elderly depressed patients. T1 relaxation times are reflective of the content and macromolecular environment of tissue water protons; shorter hippocampal T1 values may reflect differences in the content or organizational properties of hippocampal water protons. These findings are consistent with several lines of evidence that have implicated a role for the hippocampus in the regulation of mood and in the pathophysiology of the stress response, and they suggest that major depression may be associated with biophysical tissue changes in the aging hippocampus.