Fifteen patients who received courses of treatment with ACTH and cortisone were studied by interviews, psychological tests, biochemical tests and electroencephalographic studies. Neither ACTH nor cortisone causes transient deterioration of mental functioning. (It is possible that more prolonged administration may affect cerebral function.) Affective or behavioral changes were not considered to be due to toxic effects. No evidence was noted that the corticosteroids had an anesthetic effect. The euphoria noted in some patients was compatible with amelioration of physical symptoms. ACTH was more effective therapeutically and was more euphorigenic. Changes in mood were also noted where the administration of placebos was accompanied by real or subjective physical improvement. No correlations could be made between EEG changes and changes in mood. One patient with disseminated lupus did have a psychotic reaction which was clearly related to the occurrence of brain damage. The effect of the hormones in patients with illnesses that have caused brain damage may be different.