Baseline beta-endorphin and cortisol levels and their responses to 1 mg dexamethasone were measured in 11 healthy controls and in 35 depressed patients, categorized according to the DSM-III. Dexamethasone significantly suppressed beta-endorphin levels. Depressed patients with melancholia/psychotic features exhibited significantly increased post-dexamethasone beta-endorphin levels compared with healthy controls, minor and simple major depressives; the baseline beta-endorphin levels did not differ between those study samples. Post-dexamethasone beta-endorphin and cortisol values were found to be significantly and positively correlated. Accordingly, cortisol non-suppressors showed significantly higher post-dexamethasone beta-endorphin levels. Post-dexamethasone beta-endorphin may be the most sensitive and specific reflection of the disorder in negative feedback exerted by dexamethasone in depression.