Objective: To determine whether relative adrenal insufficiency (RAI) can be identified in nonseptic hypotensive patients in the intensive care unit (ICU). Design: Retrospective study in a medical-surgical ICU of a university hospital. Patients: One hundred and seventy-two nonseptic ICU patients (51% after trauma or surgery), who underwent a short 250 μg ACTH test because of > 6 h hypotension or vasopressor/inotropic therapy. Measurements: On the test day, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score were calculated to estimate disease severity. The ICU mortality until day 28 was recorded. Best discriminative levels of baseline cortisol, increases and peaks were established using receiver operating characteristic curves. These and corticosteroid treatment (in n = 112, 65%), among other variables, were examined by multiple logistic regression and Cox proportional hazard regression analyses to find independent predictors of ICU mortality until day 28. Results: ICU mortality until day 28 was 23%. Nonsurvivors had higher SAPS II and SOFA scores. Baseline cortisol levels correlated directly with albumin levels and SAPS II. In the multivariate analyses, a cortisol baseline > 475 nmol/l and cortisol increase < 200 nmol/l predicted mortality, largely dependent on disease severity but independent of albumin levels. Corticosteroid (hydrocortisone) treatment was not associated with an improved outcome, regardless of the ACTH test results. Conclusion: In nonseptic hypotensive ICU patients, a low cortisol/ACTH response and treatment with corticosteroids do not contribute to mortality prediction by severity of disease. The data thus argue against RAI identifiable by cortisol/ACTH testing and necessitating corticosteroid substitution treatment in these patients.