There is a possibility that an endogenous substance exists which interacts with a ouabain binding site on Na+, K+-ATPase. Recently, several reports have appeared suggesting the presence of an endogenous digitalis-like substance in acid-acetone extracts of brain. We have demonstrated that in preparing an acid-acetone extract, peroxidized lipids and lysophospholipids are produced, both of which inhibit Na+, K+-ATPase, thereby complicating interpretation. Preliminary evidence suggests, however, that when rat brains are extracted with an aqueous-acetone mixture under nitrogen, a principle is obtained which specifically inhibits Na+, K+-ATPase.