The experiments to be described in this and the following two papers are part of an attempt to investigate the effect of metabolic and physiologic disturbances on resistance to bacterial infections. One of the models used in our laboratory for this purpose being the experimental infection of mice with staphylococci, it proved necessary to acquire as a background more precise information concerning the natural history of this experimental disease in normal animals.While not designed for the purpose of analyzing the mechanisms of pathogenicity of staphylococci, the experiments have brought out nevertheless a number of facts relevant to this problem. They have confirmed that the intravenous injection of virulent staphylococci into normal mice commonly results in a fatal outcome due to the rapid and progressive development of abscesses in the kidney (4). As expected, the strains of staphylococci found to be virulent for mice had the ability to coagulate human and rabbit plasma in vitro (7,14,16). However they all proved coagulase-negative in mouse plasma. One unexpected finding emerged from the comparative study of several strains endowed with various degrees of virulencc namely the fact that the non-virulent, coagulasenegative staphylococci tested were not killed in vivo as rapidly and as completely as could have been assumed from the results of phagocytosis experiments in vitro published by other investigators (13,19). True enough these avirulent organisms were progressively cleared from the various organs, but hardly faster than were virulent coagulase-positive staphylococci. Like the latter, the avirulent organisms persisted for many days in the liver, lungs, and spleen--although in much reduced numbers. Even more surprisingly, they often multipled in the kidneys where they reached very large numbers in certain cases before disappearing in the natural course of events.Taken together, the results suggest that, in the mouse at least, the differences in virulence between coagulase-positive and coagulase-negative strains of