Various factors influencing toxicity of 4-nitroquinoline 1-oxide (4-NQO) in Chinese hamster ovary cells were determined. Cell density during 4-NQO treatment and volume of treatment medium had a great effect on cell survival indicating that not the 4-NQO concentration per se, but the amount of 4-NQO per cell determines the toxic effect. When the cell-cycle response for 4-NQO-induced cell killing was measured in synchronous cells, a characteristic age response was seen in wild-type cells with greatly increased sensitivity in late G1 to early S and resistance increasing through the S-phase. In contrast, a UV-hypersensitive mutant, which is also more sensitive to 4-NQO showed only minor cell-cycle variations in its response to 4-NQO. Therefore, it appears that the cell-cycle pattern observed in the wild-type cells is associated with DNA repair.