The effect of low-dose preirradiation on the susceptibility of cells to radiation was examined in normal human embryonic cells exposed to X rays. Cells became significantly resistant after low-dose preirradiation when cells were irradiated with 2 cGy of X rays 5 h before exposure to 6 Gy of X rays. We found that the frequency of giant cells in the colonies surviving 6 Gy, which was the marker for genetic instability, was slightly lower compared to cells without low-dose preirradiation. The cloning efficiencies of cells surviving 6 Gy of X rays were consistently lower than those of the control cells during the successive transfer; they were increased slightly by low-dose preirradiation, although the increase was not significant. As genetic instability is not expressed uniformly among the progeny, the effect of low-dose preirradiation was examined in individual colonies surviving 6 Gy of X rays with or without preirradiation. Genetic instability, as judged by chromosome bridge formation in anaphase in each growing colony, was reduced significantly by preirradiation (P < 0.001, Wilcoxon test), and only 39% of the colonies receiving preirradiation showed instability compared to 61% of those surviving 6 Gy of X rays alone. These results suggest that low-dose preirradiation causes an increase in the amount of DNA damage that is repaired, which potentially causes genetic instability among the progeny of surviving cells.