The aim of the present study was to examine the use of low-dose ACTH-(1-24) stimulation for assessment of adrenal function and the detection of mild adrenal insufficiency. The criteria for normal response to ACTH-(1-24) are a peak cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of the cortisol level above the basal one of more than 200 nmol/L (7.2 micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2) than the dose of 250 micrograms in the standard test. At 20 min, the peak cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/- 1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/- 1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%) failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL) following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%) showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16 patients, showing insufficient response to low-dose ACTH-(1-24), also had a significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/- 10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h). Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed normal stimulation with the standard 250 micrograms ACTH test. Therefore, it appears that a low-dose ACTH test is capable of revealing mild adrenal insufficiency, which is not detected by the standard high-dose ACTH test.