Changes in the radiation age response are described in two cell lines derived from human squamous cell carcinomas. A radioresistant tumor cell line, JSQ-3, has a DO of 240 cGy and is polyploid with a DNA content of 2.68. A relatively radiosensitive tumor cell line, SCC-61, has a DO of 126 cGy and has a DNA index of 1.16. Tumor cells were separated and synchronized by centrifugal elutriation; flow cytometry was used to determine cell-cycle parameters and relative synchrony. The radioresistant cell line, JSQ-3B, was found to have twice the number of cells in S-phase than the more sensitive cell line (28% and 13% for JSQ-3B and SCC-61B, respectively). Both cell lines, despite differences in intrinsic radiosensitivity, were most resistant during S-phase (DOs of 258 and 157 cGy for JSQ-3B and SCC-61B, respectively) and were maximally sensitive during G1 (DOs of 193 and 95 cGy for JSQ-3B and SCC-61B, respectively). Clinical implications of our findings are discussed.