Objective: To investigate the adrenocortical function in brain-dead patients, potential organ donors. Design: Prospective study. Setting: Intensive care units in two teaching hospitals. Patients: A total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42+/-18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. Interventions: In all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 mug of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n=10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 mug/dL after the administration of adrenocorticotropic hormone were defined as responders. Measurements and Main Results: After the occurrence. of brain death, group B patients had significantly lower values for baseline (8.5+/-6.2 vs. 17.0+/-6.6 mug/dL, p<.001) and stimulated (16.9±6.3 vs. 23.9±5.7 μg/dL, p=.001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p<.001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r=.71, p=.001), whereas there was no correlation, between baseline cortisol and the increment in cortisol (r=-.37, p=.15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5+/-11.4 vs. 6.8+/-4.2 mug/dL, p=.003) and stimulated serum cortisol (28.8+/-9.9 vs. 16.3+/-4.3 mug/dL, p=.008). Conclusions: Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.