OBJECTIVE: To evaluate the utility of cosyntropin 1 μg in assessing adrenal function in critically ill patients. DATA SOURCES: A computerized literature search using MEDLINE, EMBASE, International Pharmaceutical Abstracts, and the Cochrane Database (1966–August 2004) was undertaken for trials evaluating cosyntropin 1 μg using the following search terms: adrenocorticotropin-releasing hormone (ACTH), cosyntropin, adrenal insufficiency, cortisol, corticosteroids, glucocorticoids, sepsis, septic shock, diagnosis, critically ill, intensive care, and critical care. STUDY SELECTION AND DATA SYNTHESIS: Identifying patients with sepsis with relative adrenal insufficiency (AI) using cosyntropin testing may identify those likely to benefit from corticosteroids. The results of 5 heterogeneous studies in non—intensive care unit (ICU) patients suggest that both 1 μg and 250 μg of cosyntropin stimulate similar cortisol responses and that testing using both doses correlates well with results from insulin tolerance testing. Some data from non-ICU patients suggest that the 1-μg test may be more sensitive to detect AI; 3 heterogeneous studies in ICU patients confirmed the improved sensitivity of the 1-μg test. CONCLUSIONS: Use of cosyntropin 1 μg should detect AI in all patients who would have been diagnosed using 250 μg. Unfortunately, all of the clinical trials evaluating the role of corticosteroids in septic shock that used the cosyntropin stimulation test administered 250 μg. Extrapolation of the existing guidelines to treat patients with septic shock testing positive for relative AI using the 1-μg test may provide effective therapy to appropriate patients not diagnosed by the 250-μg testing or may introduce additional adverse effects in patients who should not receive corticosteroids. Large-scale, head-to-head comparison data of steroid effectiveness after 1- and 250-μg ACTH stimulation tests are needed to expand upon these promising results.