Previous studies have demonstrated that the injection of homologous hemolyzed blood, and reticuloendothelial system (RES) clearance of the erythrocyte membrane debris, depress RES phagocytic function and increase shock susceptibility. This study was carried out to determine if the degree of intravascular hemolysis following experimental thermal injury was comparable to the dose of hemolyzed blood required to depress RES function. The IV injection of graded doses of hemolyzed blood into rats demonstrated that 0.2 mg/100 gm of hemolyzed blood was the minimum dose of hemolyzed blood which would cause an RES depression. This volume of hemolyzed was equivalent to 2.8% of the blood volume of the animals studied. Hemolysis was assessed from the plasma hemoglobin and blood volume following graded thermal injury in anesthetized animals. Thermal injury which caused an 80% mortality rate was associated with the acute hemolysis of 3.1% of the blood sufficient erythrocyte membrane debris to induce RES depression and therapy impair host defense.