Hyperglycemia and hypoxia acidosis are known to occur during periods of shock. The plasma levels of catechol amines have been reported to be elevated during periods of shock. Injection of epinephrine or levarterenol can produce increments in blood glucose and have been shown to elicit a metabolic acidosis. In the present studies the effects of reducing circulating blood volume or infusion of lactic acid and of forced CO2inhalation on ventricular isometric systolic tension (VCF) and the cardiovascular response to test injections of levarterenol were studied. The experiments with a reduction in circulating blood volume and with lactic acid infusions resulted in a decrease in arterial pH. whole blood total CO2and whole blood CO2combining power. Concomitant with these changes there was a marked depression of VCF and the response to test injections of levarterenol. Correction of the acid-base changes with 2-amino-2-hydroxymethyl, 1, 3-propane diol resulted in an immediate improvement in VCF and in the response to levarterenol. This change occurred despite a greater increase in blood lactate levels. Anaerobic metabolism with lactate production leads to a decrease in total blood CO2and an increase in dissolved CO2. This decrease in the CO2-carrying capacity would lead to an increase in tissue CO2. Since the heart is markedly depressed by CO2, this increment could be largely responsible for the myocardial depression. The oxygen debt which the heart can incur is thought to be limited. Therefore, the build-up of CO2one of the end-products of aerobic metabolism, would depress oxidative metabolism according to the law of mass action. This hypothesis was further tested by forced CO2ventilation which resulted in a marked depression of VCF and the response to levarterenol. Correction of the respiratory acidosis by the administration of THAM which increased the CO2-carrying capacity of the blood resulted in an immediate improvement in VCF and the levarterenol response.