Adrenocortical insufficiency is a serious complication of AIDS. Usually, integrity of the hypothalamo-pituitary-adrenal (HPA) axis in AIDS patients is assessed by measuring basal cortisol levels and cortisol response to 250 g of ACTH. Recent studies suggest that a lower ACTH dose increases the sensitivity of the procedure. In the present study, we investigated the prevalence of adrenal hypofunction in AIDS patients using a low-dose ACTH test (1 g), evaluated the clinical characteristics that might suggest this diagnosis, and the diseases and/or drugs that could be associated with it. We prospectively evaluated 63 very ill AIDS patients and 16 normal controls. A standard examination assessed the presence of signs and symptoms of adrenal insufficiency. Blood samples were collected before and 30 and 40 minutes after an injection of 1 g 1-24 ACTH. No opportunistic disease, signs, symptoms or drugs were associated with an abnormal cortisol response to ACTH. The lowest stimulated cortisol level in the control group was 18.5 g/dL; cortisol levels ≥18 g/dL were taken to indicate a normal HPA axis. Test results revealed that 12/ 63 AIDS patients (19%) had an abnormal HPA axis. With these data in mind, we suggest a prospective adrenal function evaluation of all severely ill AIDS patients.