Pretreatment measures of hypothalamic-pituitary-adrenocortical (HYPAC) function in depressed, manic, and healthy normal subjects showed that nonsuppression on the dexamethasone suppression test (DST) had less positive predictive value for major diagnostic category and was more frequent in normals (8/77) than recently reported, although it was yet more frequent in depressed patients (35/111). Nonsuppression was common in manics (8/16), was similar in unipolar and bipolar depressed patients (35% and 27%, respectively), and did not segregate with melancholic, endogenous, or psychotic depression subtypes. Patterns of post-DST plasma cortisol concentration other than simple escape or nonescape from suppression were common. Nonsuppression of 9 AM plasma cortisol levels on the DST had as good or better diagnostic specificity as nonsuppression of any of three post-DST samples. Nonsuppression was not completely synonymous with HYPAC hypersecretion. Means of pre-DST HYPAC measures (morning plasma cortisol, urine free cortisol, and CSF cortisol levels) were elevated in depressed patients compared with normals. There were significant differences in HYPAC measures of depressed patients studied at different centers. Age correlated positively and body weight negatively with plasma cortisol level.