Sf9, a lepidopteran cell line isolated from the fall armyworm, Spodoptera frugiperda, was shown to be significantly more resistant to growth inhibition and apoptosis induction effects of x-ray irradiation than several human cell lines of different origins. The single-cell electrophoresis technique revealed that Sf9 cells showed lower x-ray irradiation-induced DNA damage as well as better efficiency at repairing these damages. In addition, Sf9 cells were lower in both background and x-ray irradiation-induced intracellular oxidative stress, in which the higher intracellular level of reduced glutathione seemed to play a major role. The significance of oxidative stress in determining the radioresistance of Sf9 cells was confirmed by their being more resistant to hydrogen peroxide while equally susceptible to other non-reactive oxygen species of N-nitroso alkylating agents when compared with a human cell line. Although the Sf9 and human cell lines were equally susceptible to the lethal effects of N-nitroso alkylating agents, the components of DNA damage-induced and the repair enzymes involved significantly differ. This phenomenon is also discussed in this report.