The direct effect of ACTH on brain tissue not by way of adrenal glands is suggest by the fact that ACTH has a remarkable therapeutic effect on vairous diseases of nervous system such as japanese encephalitis. The first part of the present report is concerned with statistical observation of therapeutic effect of ACTH on patients with nervous diseases. 1) ACTH was effective in 70 per cent. The effect was especially marked in Parkinson's syndrome, japanese encephalitis and chorea minor. 2) As for symptoms, disturbance of consciousness, fever, involuntry movements and mucle rigidity were successfully treated by ACTH. 3) In intracranial bleeding and thrombosis too, ACTH showed a good effect on loss of consciousness, motor disturbance and dysarthria in a decreasing order. The second part is concerned with observation of therapeutic effect of ACTH on brain edema of adrenectomized dogs. Degree of edema is calculated by the amount of RIHSA measured in the brain. 1) In the control, index of brain edema (amount of isotope of brains cortex of the thrombosed side/that of the contralateral normal cortex) was 15.6 2) In dogs removed of adrenal cortex & treated by ACTH, index of brain edema was 6.4. The above results indicate that ACTH has a dirct effect, not by way of adrenal cortex. It is clarified, however, whether this effect is a direct on brain tissue or by an enhancement of coricosteroid effect.