Cardiac arrest produces a prompt and maximal increase of plasma catecholamines, with associated elevations of the hormones involved in the endocrine response to stress. To investigate the participation of the central nervous system (CNS) in the generation of the endocrine response, the catecholamines epinephrine and norepinephrine in cerebrospinal fluid (CSF) were measured before, during, and after cardiac arrest accompanied by cardiopulmonary resuscitation (CPR) in adrenalectomized (ADX) and sham-operated (SHAM) dogs. We also determined the activity of acetylcholine esterase (AChE), an intracellular enzyme released into the CSF after hypothalamic or caudate stimulation. During CPR, plasma epinephrine increased significantly in SHAM but not ADX dogs, increasing from (mean +/- SE) 480 +/- 171 to 29,800 +/- 14,200 pg/ml (P less than 0.05). Prearrest CSF norepinephrine was higher in ADX than SHAM dogs and increased in both groups with cardiac arrest, but the increase was significant only in SHAM animals; CSF epinephrine remained unchanged during or after cardiac arrest. CSF AChE activity increased during and after defibrillation; the difference with basal levels became significant when the peak postarrest values were considered (P less than 0.05). These results document biochemical changes occurring in the CNS during maximal stress represented by cardiac arrest. It is suggested that CSF norepinephrine and AChE activity elevations are markers for hypothalamic activation from the stress of cardiac arrest.