Summary The action of tetracycline, oxytetracycline, chlortetracycline, chloramphenicol and streptomycin, was studied on 131 strains of Shigella flexneri isolated during the years 1953, 1955, 1956, and 1957. None of the 31 strains of Shigella flexneri tested in 1953 was resistant to tetracyclines. Among the strains isolated during the years 1955, 1956, and 1957, 19%, 34%, and 39%, respectively, were resistant to these antibiotics. The possible relationship between the emergence of the resistant strains and the extensive use of tetracyclines during the period of study is discussed. A similar phenomenon was observed in the case of chloramphenicol, though not as striking as in the case of tetracycline. With streptomycin the opposite situation occurred. The concentrations of tetracyclines and chloramphenicol required to inhibit growth of most of the susceptible strains of Shigella tested was smaller than that required with streptomycin. Among the various serotypes of Shigella flexneri studied there was not a significant difference in resistance to tetracyclines, while with chloramphenicol, and streptomycin there were certain serotypes which were more resistant than others.