In order to study the mechanism of shock produced by local anesthetics, secondary actions caused by local anesthetics in the part of living bodies were investigated. The following results were obtained: 1. Two of the anesthetics, nupercaine and tetracaine, easily produced free base in alkaline solution. By mixing the two anesthetics with serum protein, it was found that they aggregated with it by incubation at37°C for24 hours. 2. As the result of analysis by means of ultraviolett resorption spectrum and paper electrophoresis, those aggregated substances proved to be denatured protein which belong to serum globulin. 3. As the result of quantitation by microprotein method, the protein content of the aggregated protein, produced by0.2% solution of nupercaine and tetracaine each, with equal volume of normal rabbit serum, was found to be severally800γ and 132γ per ml. 4. Among the anesthetics, nupercaine, tetracaine and procaine showed distinct hemolytic action in0.5% concentration and upward. Especially nupercaine showed nearly equal hemolytic action as saponine, which is hemolytic toxicum. 5. Nupercaine and tetracaine showed remarkable increase of capillary permeability, and this action was definitely inhibited by preliminary treatments of antihistamic and antiserotonic. 6. Every anesthetics, especially nupeacaine, caused disruptive action on mast cells. In the case of nupercaine, the changes of mast cells count in the mesentery of rats were found to be most remarkable. Next tetracaine, and then the case of procaine. 7. The fall of blood pressure, a reaction of local anesthetics, has a correlation with histamine liberating action from blood plasma in vitro. The greater the action, the greater the degree of the fall of blood pressure. By repeated intravenous injections of local anesthetics, tachyphylaxis phenomenon was observed in the fall of blood pressure. The preliminary treatments by means of antihistamic controled the fall of blood pressure.