Summary1. The repetitive daily administration of epinephrine in the dog results in a progressively diminished eosinopenic response.2. During the state of epinephrine resistance, there is neither a depletion of endogenous ACTH nor an exhaustion of the adrenal cortex.3. Adaptation of the organism to epinephrine stress with decreased tissue utilization of corticoids seems to most satisfactorily explain the phenomenon of epinephrine resistance at the present time.4. Demonstration of resistance to epinephrine speaks against epinephrine as the only physiological stimulus for the continuous secretion of ACTH.