Summary and Conclusions: Broth filtrates of a pathogenic hemolytic streptococcus contain a substance, “leucocidin”, already described, that causes loss of phagocytic power, visible morphological changes, and loss of the power to reduce methylene blue in leucocytes of certain types and of certain animal species in varying degree. Rabbit clasmatocytes, or connective tissue macrophages, reduce methylene blue in equivalent numbers better than do polymorphonuclear cells from the same animal. A comparison of exudates of essentially similar cell type from the dog, guinea pig and rabbit indicate that the first two exceed the exudate of the latter animal in reducing power. The mononuclear cells (clasmatocytes) of the susceptible rabbit are found almost completely resistant to streptococcus leucocidin as contrasted with polymorphonuclear cells from the same animal which are completely destroyed. Dogs and guinea pigs are very resistant to infection with our rabbit strain of streptococcus. The leucocytes of these animals are likewise almost completely resistant to our leucocidin which is so destructive for rabbit polymorphonuclears. There is apparently, then, a direct relationship between natural species resistance and enhanced resistance in a susceptible species to a given streptococcus, and the differential resistance of the cells of these species or individuals to streptococcus leucocidin. Varying conditions of growth of the streptococcus culture have been tried in producing leucocidin. Plain infusion broth, with or without peptone, produces an active filtrate. The addition of rabbit whole or laked blood may increase leucocidin production but introduces certain complications. Varying amounts of leucocidin are found in cultures grown from six hours to fourteen days, the most potent filtrates being found in cultures aged from eighteen to forty-eight hours. This is not to be confused with production of acid which was controlled. There would seem to be a direct relationship between leucocidin produced by different streptococci and their pathogenicity provided the leucocytes under consideration are of a species against which the pathogenicity is operative. Our tests however are limited largely to rabbit cells and to strains of varying pathogenicity for rabbits. Streptococcus leucocidin can be concentrated by evaporation and even dried without deterioration. It is relatively thermostable (70°C. for one hour). There is evidence, however, that it is readily oxidized. Streptococcus leucocidin is separable from streptococcus hemotoxin, as shown by its earlier production and far greater persistence in culture filtrates, and by its greater thermostability. Leucocidin affects the reducing power of cells other than leucocytes. Fresh rabbit tissues reduce methylene blue in varying degree: Brain, testicle, kidney, liver, adrenals, muscle and, to a less extent, lung, are reductive; spleen and bone marrow almost completely lack reducing power. The more strongly reducing tissues vary in their susceptibility to streptococcus leucocidin, adrenal, muscle and lung being largely unaffected. Preliminary experiments indicate that we are not dealing with a series of specific “cytocidins” but with the more general action of a single substance. In spite of its marked effect on leucocytes and other tissues, the most potent leucocidin we have obtained may be given rabbits in relatively large amounts intravenously without obvious effect. We have not been able to enhance the pathogenicity of a nonvirulent streptococcus by adding leucocidin from a virulent strain. The serum of the naturally resistant guinea pig neutralizes our leucocidin in marked degree. Rabbit serum only in exceptional instances shows a neutralizing effect. Antistreptoleucocidin may be produced in the rabbit but only by using as antigen the pleural exudate of rabbits dead of infection which contains leucocidin in greatest concentration.