The authors investigated four aspects of central control of adrenal cortical activity and three aspects of peripheral metabolism. Their results suggest that the central control mechanisms function normally during depression, but the peripheral measures of cortisol activity revealed interesting abnormalities. During depression, both the production rate and the metabolic clearance rate were elevated, but a normal 24-hour mean plasma cortisol concentration was maintained. On recovery, the production rate fell while the metabolic clearance rate remained high, resulting in a low plasma cortisol concentration. The authors also discuss the implications of investigating cortisol dynamics with radio-isotope dilution methods.