1. Six indices of adrenal cortical activation have been compared in groups of normal male subjects and schizophrenic male patients when they were subjected to a variety of stresses. The indices are changes in output of urinary sodium, potassium, uric acid, 17-ketosteroids and neutral reducing lipids together with changes in the number of circulating lymphocytes. The stresses have been the target ball frustration test, operation of a pursuit meter (each test lasting one hour), the effects on our indices of adrenal cortical extract and of pituitary adrenocorticotrophin.2. Responses of our 6 adrenal cortical indices and also eosinophile responses to injected adrenocorticotrophin were determined for groups of male and female psychoneurotic patients and compared to normal controls.3. The tests all involved significant numbers of patients and controls and the results have been treated statistically.4. Our data indicate a highly significant failure of normal adrenal stress responses in the schizophrenic population as compared with the control population.5. The failure occurs principally at the level of the ability of the adrenal cortex to respond to adrenocorticotrophin.6. This failure was not corrected by a dietary supplement rich in proteins and vitamins.7. These findings are discussed in relation to the etiology of schizophrenia.8. Psychoneurotic patients in contrast to schizophrenics respond in a normal fashion to injected adrenocorticotrophin.Abstract Teaser