A total of 10 patients who fulfilled DSM-III-R criteria for major depression were recruited to the study, each of whom had failed to respond to a 6-week course of treatment with either sertraline or fluoxetine. Each subject had baseline serum cortisol measurements together with a Hamilton depression (HAMD) score. All patients were started on dexamethasone (3 mg daily) for 4 days, while remaining on their antidepressant treatment. Further Hamilton ratings were made on days 5 and 21. Six patients showed a significant improvement, whilst two showed a minimal response. A good clinical response was associated with a high baseline cortisol level.