Despite the great clinical importance of the low-dose dexamethasone suppression test (determination of cortisol after dexamethasone 2 mg p.o. at 11.00 p.m. in the evening before) and of the determination of ACTH in plasma, so far only little is known about the ACTH response to dexamethasone in normal subjects. In the present study cortisol and ACTH were determined by radioimmunoassay in normal subjects at 8.00 a.m., 10.00 a.m. and noon before and after dexamethasone. Additionally the cortisol response to ACTH was tested under both conditions. The ACTH concentrations in the morning show a periodicity quite similar to the well-known circadian rhythm of cortisol secretion. Dexamethasone blocks this periodicity without decreasing ACTH significantly. The cortisol response to ACTH after dexamethasone is normal. In the morning only a basal and presumably biologically inactive ACTH is secreted which can not further be suppressed by dexamethasone. Therefore it is advisable for the diagnosis of hypercortisolism to measure ACTH only in stimulation tests, e.g. insulin-induced hypoglycemia.