A factor capable of lysing erythrocytes arose in the plasma of various strains of mice when the plasma was incubated at 37 degrees C. The hemolytic activity and the amount of lysophosphatidylcholine (lysoPC) in the plasma reached a maximum at 3 h of incubation. Both the hemolytic activity and the increment portion of lysoPC were recovered from the prealbumin fraction on agarose gel electrophoresis. Serum albumin, an inhibitor of the hemolytic action of lysoPC, inhibited the hemolytic action of the this factor. These and other results indicate that the hemolytic factor is a lipoprotein that contains lysoPC as an active site. The molecular weight of active fraction was distributed from 100 000 to 200 000. The finally purified fraction contained 65% protein composed of a polypeptide with a molecular weight of 25 000. The lipid composition of this fraction was 12.4% lysoPC, 63.9% phosphatidylcholine (PC), 5.4% sphingomyelin, 2.1% triacylglycerols and 16.2% cholesterol. This hemolytic lipoprotein was also found in the prealbumin fraction when electrophoresis of plasma of the lysoPC-administered mice was carried out. However, such lipoprotein was not formed by simple addition of lysoPC to the nonincubated plasma.