Hypothalamic hormones as well as anterior pituitary hormones were detected in the peripheral plasma after the diagnosis of brain death. It is possible that residual hypothalamic tissue was functioning after satisfying the usual criteria of total brain death. To examine this possibility, endocrinological and morphological alterations of the hypothalamic-pituitary system was evaluated in 28 brain dead patients. Intrinsic ADH was depleted in the plasma shortly after the diagnosis of brain death. Anterior pituitary hormones were initially detected in all patients, but gradually disappeared. The direct TRH (thyrotropin releasing hormone) stimulation to the anterior lobe was responded to well. Morphological studies showed a partial necrosis of the anterior lobe and the preservation of the posterior lobe for as long as a week. These data prove that the pituitary is partially preserved after brain death. LH-RH (luteinizing hormone releasing hormone) was detected in the peripheral plasma of all patients and GRF (growth hormone releasing factor) was detected in half of the patients for as long as 15 days, but autopsy revealed the fact that the brain tissue including the hypothalamus became extensively necrotic after the sixth day of brain death. In order to solve this controversy it is proposed that these hormones originate from extracranial tissues such as pancreas. The detection of hypothalamic hormones after the diagnosis of brain death therefore is not contradictory to the concept of total brain death.