Studies were carried out in dogs and rabbits subjected to hemorrhagic and tourniquet shock to determine the tissue origins of two newly described vasotropic principles, VEM and VDM. The vasoexcitor principle, VEM, predominates in the blood during the initial compensatory stage and was traced to the kidney. The vasodepressor principle, VDM, prevails during the decompensatory phase and was found to originate in the liver, skeletal muscle and spleen. During the decompensatory phase, there was a progressive deterioration of the hepatic mechanisms for inactivating VDM. Sequential tissue hypoxia during shock is probably responsible for the formation of these vasotropic principles and for the deterioration of the hepatic VDM inactivation system. Special emphasis is placed on the effects of local concentrations of VDM within the liver and on the resultant diversion of blood from the general circulation into the splanchnic viscera.