Magnetic resonance images centered at the pituitary stalk were used to measure pituitary gland size in 19 patients with major depression compared with that in age- and sex-matched controls. Depressed patients had significantly greater pituitary cross-sectional area (P = 0.0009) and volume (P = 0.007) than the controls. This difference was particularly prominent in elderly depressed patients compared to elderly controls. These results provide the first demonstration of structural alterations in the pituitary gland in major depression.