Normal mammalian sera contain the heat labile opsonin system that promotes the phagocytosis of various microorganisms by polymorphonuclear leukocytes. Because the heat labile opsonin system is present in normal nonimmune sera and because it operates against various microorganisms in an apparently nonspecif manner, it is considered to play an important role during the early phase of an acute bacterial infection. The role of various factors participating in the heat labile opsonin system, and its in vivo significance are discussed.