Earlier work has suggested that the decreased cardiac performance in shock is due to negative inotropic substances that alter the Ca++ metabolism of the myocardium. We investigated this possibility by examining the Ca++-dependent ATPase activity and the Ca++-uptake ability of cardiac sarcoplasmic reticulum (microsomes) from normal hearts and endotoxin-shocked hearts. Both the ATPase activity and the accumulation of Ca++ by microsomes from shocked hearts were lower than for microsomes from normal hearts. In the presence of serum from shocked dogs, the ATPase activities and Ca++-uptake of both microsome preparations were reduced from those measured in modified Krebs-Henseleit, but this was not considered significant because the same extent of depression was seen with serum from normal dogs. These findings could not attribute the depressed ATPase activities and Ca++-uptake abilities to a shock-induced circulating cardio-depressant material but did demonstrate that calcium metabolism in cardiac tissue was altered in the shock state.