To determine whether somatostatin is found in the hypothalamus and extrahypothalamic brain, we studied autopsy brain tissue by specific immunoassay. The hypothalamus contained the highest concentration (16.7±2.4 S.D. pg per microgram of protein), with small amounts in brain-stem, cerebral cortex, cerebellum, pineal gland and spinal cord. Cerebrospinal fluid of seven neurologically normal persons also contained somatostatin in concentrations ranging from 15 to 55 pg per milliliter. To determine whether brain disease leads to abnormal cerebrospinal-fluid somatostatin, we examined 30 patients with neurologic disease, of whom 20 of 24 with cord or cerebral disease had concentrations above the highest normal level. The wide variety of diseases with somatostatin elevation suggests nonspecific leakage from damaged brain tissue. Cerebrospinal-fluid somatostatin may provide a good index of brain damage. Although correlated statistically with cerebrospinal-fluid protein, somatostatin concentration in five of 24 cases exceeded the upper limit of normal by 3 S.D. while protein was normal. (N Engl J Med 296:529–533, 1977)