The relative responses of V79 and V79/79 cells to mutation to 6-thioguanine (6TGR) and ouabain resistance (OUAR) have been compared in unmutagenized cells and after exposure to ethyl methanesulphonate (EMS), N-methyl-N-nitrosourea (MNU) and ultraviolet light. In the V79/79 cell line, the spontaneous frequency of 6TGR colonies but not of OUAR colonies was enhanced compared to that in V79 cells. This appears to be the result of a reduced growth rate and plating efficiency of V79/79 cells and does not reflect a real difference in spontaneous mutability. V79/79 cells were more sensitive than V79 to the cytotoxic effects of all three mutagens, but induced mutation by UV, EMS and MNU to 6TGR was similar in the two cell lines. The lack of a differential response for induced mutation to 6TGR may reflect: (a) differences in selective stringency of thioguanine in the two cell lines, and (b) the greater susceptibility of V79/79 cells to induced chromosome damage. The relative mutability of the two cell lines to OUAR was dependent on the mutagen used. V79 cells were significantly more mutable than V79/79 cells after MNU exposure, but the two cell lines were similar in sensitivity to EMS-induced mutation. After UV-irradiation, however, V79/79 cells were morem utable than V79 cells. The differential response of the two cell lines to MNU suggests that O6-methylguanine is potentially mutagenic in V79 cells but is both potentially lethal and potentially mutagenic in the more sensitive V79/79 cells. The absence of a differential response to EMS-induced mutagenesis suggests that methylated and ethylated bases are repaired differently in Chinese hamster cells. The hypermutability of V79/79 cells by UV-irradiation indicates that thymine dimers are potentially lethal and potentially mutagenic in both cell lines.