The goal of this study is the characterization of those rickettsial constituents which permit Richettsia rickettsii to successfully invade and multiply within the tissues of man and laboratory animals. Six strains of R. rickettsii were classified into three virulence groups on the basis of the ability of the rickettsiae to produce disease in guinea pigs. Differences n representatives of these virulence classes were demonstrated by radioimmune precipitation of extracts of the rickettsiae surface-labeled with 125I.