The effect of two representative plasmids, R100 and F8-gal, on the susceptibility of Escherichia coli to kasugamycin was studied. R + and F + cells were found to be more susceptible to this antibiotic than R − and F − cells, respectively. Retransfer and curing experiments of these plasmids show that this increased susceptibility of host cells to kasugamycin was conferred by either of the plasmids. At the early stage of growth of R100 + cells in the presence of kasugamycin, R − segregants overgrew the population and then they were replaced by kasugamycin-resistant mutants of the R + cells which became the majority cell line of the population. The former phenomenon is assumed to be due to the increased susceptibility of R100 + cells to kasugamycin, and the latter is probably related to the finding that R100 enhances the spontaneous mutation of host cells to resistance to kasugamycin. The practical and experimental significance of these findings are discussed.