In an attempt to validate several subtypes of affective disorders, 52 consecutive patients hospitalized at a clinical research center were comprehensively classified along several diagnostic and phenomenologic axes. Cortisol levels of each patient were evaluated at baseline and after the administration of 0.5 and 1.0 mg dexamethasone. None of the depressive subtypes responded significantly differently to the 1.0 mg dose. However, the bipolar subtype was associated with significantly different DST responses to the 0.5 mg dose. Patients with bipolar affective disorder, both manic and depressed, had higher postdexamethasone mean cortisol levels than all other groups. The results support the distinctiveness of the bipolar diagnosis.