This study of 33 normal adult males investigated the nature of relationships between plasma cortisol levels and depression. Both plasma cortisol levels and responses to the Dexamethasone Suppression Test (DST) have been shown to be associated with clinical depression. However, relatively few studies have investigated the utility of either plasma cortisol measures or the DST for evaluating emotional distress in subjects without demonstrable psychiatric morbidity. The results of this study suggest that the traditional DST has little discriminatory power when used with psychologically healthy subjects. Conversely, plasma cortisol was shown to be positively correlated with clinical personality characteristics associated with emotional distress, particularly depression. These data suggest the hypothalamo-pituitary-adrenal irregularities are not only associated with clinical psychopathology but may also be related to emotional reactivity in normal, asymptomatic individuals.