BACKGROUND: Insulin induced hypoglycemia has been used to assess the adrenocortical function, but may be hazardous. The standard rapid ACTH stimulation test has been advocated as a substitute but is sometimes insensitive. In this study, low dose (1ug) rapid ACTH stimulation test was compared to insulin induced hypoglycemia and standard dose (250ug) rapid ACTH stimulation. METHODS: 27 patients (14 men and 13 women) with pituitary disease and definite adrenocortical dysfunction (14 patients were confirmed by insulin induced hypoglycemia) and 23 controls (pituitary control: 3 men and 7 women, confirmed by insulin induced hypoglycemia, normal control: 8 men and 5 women) were studied. All subjects underwent rapid ACTH stimulation test with 2 different level of stimulation (1 and 250ug). Serum cortisol levels were measured at 0, 30 and 60 min after each dose of ACTH injection. A normal response was defined as a peak cortisol value of 497nrnol/L (18ug/dL) or above, RESULTS: During rapid ACTH stimulation study in controls, the peak serum cortisol level was significantly lower (690+-25lnmol/L (25.0+-9.1ug/dL) vs. 933+-257nmol/L (33.8+-9.3ug/dL); p< 0.01) and the peak appeared earlier (30min. vs. 60min) after the administration of low dose ACTH than after standard dose. However, the serum cortisol level at 30min was not different. In patient group, each serum cortisol level at 30min and 60min had no difference between low and standard dose (p>0.1). None of these 27 patients showed normal response to low dose stimulation, but 2 of 27 did to standard dose. In controls, 19 of 23 showed normal response to low dose, and all of 23 did to standard dose (sensitivity 100% vs 92.5%, specificity 82.5% vs 100%). The results of low and high dose stimulation test agreed with those of insulin induced hypoglycemia (Kendalls g= 0.50 vs 0.92, p<0.01 vs 0.001). CONCLUSIONS: The results of a low dose (1ug) rapid ACTH stimulation test showed good correlation with those of the standard dose (250ug) rapid ACTH stimulation test and insulin induced hypoglycemia. Thus it may be used in screening for the diagnosis of adrenal insufficiency.