The relationship between dexamethasone suppression test (DST) results and in vivo pituitary volume was studied in 24 psychiatric inpatients. The principles of systematic stereology were used to measure pituitary volume from 3-mm contiguous sagittal spin-echo magnetic resonance (MR) images of the brain. There was no correlation between pituitary volume and 3 p.m. or 10 p.m. postdexamethasone (post-DEX) plasma cortisol concentrations. However, when multiple regression analysis was performed to relate pituitary volume to gender, age, and post-DEX plasma cortisol concentrations, there was a significant relationship between pituitary volume and age, gender, and 10 p.m. post-DEX cortisol plasma concentration. This is the first study to demonstrate a method that directly measures, rather than estimates, in vivo pituitary volume. Furthermore, it suggests that activation of the hypothalamic-pituitary-adrenal axis in psychiatric patients, as manifested by elevated post-DEX cortisol concentrations, may influence pituitary volume.