Severely depressed patients frequently show inadequate suppression of serum cortisol levels by dexamethasone. In a study of 15 depressed patients, we found a robust correlation between plasma levels of cortisol and 3-methoxy-4-hydroxy-phenylglycol after dexamethasone administration. These results suggest that dexamethasone resistance and adrenergic activation reflect parallel responses to illness-related stress in some depressed patients.