The hyperergic reaction provoked in the rat by the intraperitoneal injection of egg albumin can be topically inhibited by a previously produced local inflammation. 2. The topical protection phenomenon can be modified by local and general influences. The section of the sciatic nerve of the injected leg prevents or diminishes the protecting effect. The extirpation of the suprarenal glands prior to the application of the locally irritating substance prevents the topical protection phenomenon, which reappears if the animals receive immediately after the action of the locally irritative agent an intraperitoneal injection of cortisone. 3. The topical protection phenomenon depends partly on the moving, from the blood to the tissues, of the corticosteroids which are freed during the alarm reaction following the local inflammatory irritation; these corticosteroids have an antiinflammatory action which diminishes or prevents the development of phlogistic alterations in the tissues which previously have suffered an inflammation.