In human immunodeficiency virus infected individuals, human cytomegalovirus (CMV) remains a significant pathogen. The adrenal gland is a preferential site of CMV disease in acquired immunodeficiency syndrome (AIDS) patients. However, glucocorticoid replacement is often not selected because of the risk of exacerbating underlying infection. To evaluate the need for glucocorticoid replacement in these patients, we performed a prospective study to investigate the adrenal function in 60 advanced AIDS patients. Their adrenal function including rapid ACTH test (RAT), basal plasma ACTH level, and daily urinary free cortisol level was evaluated. Approximately 25% of the patients turned out to be abnormal in this evaluation. Almost 60% of the patients could be followed up for one year or until their death. Using the follow-up data, we calculated sensitivity, specificity, positive predictive value and negative predictive value. Excretion of urinary free cortisol with normal RAT was comparable to normal controls, whereas patients with abnormal RAT excreted significantly lower urinary free cortisol. During hospitalization, 14 patients with normal RAT had febrile episode. During the febrile period the concentration of the urinary free cortisol level increased by 2.2 times. This study suggests that glucocorticoid replacement is necessary for AIDS patients suspected as clinically adrenal insufficiency, and that the dose of glucocorticoid replacement might be increased during sick days in AIDS patients with abnormal adrenal function.