BACKGROUND: In animals, stress and corticosteroids can be associated with both reversible and irreversible changes in the hippocampus. Changes in memory and hippocampal structure, perhaps in part due to cortisol elevations, are reported in some patients with mood disorders. Minimal data are available on the effects of long-term exposure to corticosteroids on the human hippocampus. We previously reported greater depressive symptom severity, poorer memory and smaller hippocampal volumes in patients with asthma or rheumatic diseases receiving long-term prednisone therapy than in controls.