• The dexamethasone suppression test (DST) as now commonly carried out in psychiatric settings yields "abnormal" results in many conditions including the healthy state. To determine whether the DST accurately identifies patients with physiologically meaningful increases in pituitary-adrenocortical activity, we compared DST results to baseline urinary cortisol level. Thirty-four psychiatric inpatients underwent a 24-hour urine collection and then a DST using 1 or 2 mg of dexamethasone. With the common 1-mg DST, 24-hour urinary cortisol levels in nonsuppressors and suppressors did not differ. With the 2-mg DST, however, nonsuppressors had significantly higher urinary cortisol levels than suppressors, and all nonsuppressors had urinary cortisol levels above the normal range. Thus, the 1-mg DST may not identify the heuristically important subgroup of psychiatric patients who have a pathophysiologically meaningful alteration in pituitary-adrenal regulation.