The relative sensitivities of a human diploid fibroblast strain (AG1522) and an established line of contact-inhibited mouse embryo fibroblasts (10T1/2) were compared after incorporation of [3H]thymidine or [125I]iododeoxyuridine into the cellular DNA and growth at 37 degrees C. Whereas these cells show similar sensitivities to acute X irradiation, the D0 for clonal survival of the mouse fibroblasts was 5- to 10-fold higher than the D0 for the human fibroblasts for both 3H and 125I. A large difference in sensitivity between these two cell types was also seen after protracted irradiation from 3H2O at 37 degrees C, but this difference was markedly reduced when cells were exposed to 3H2O at 0 degree C to simulate an "acute" irradiation. An established human tumor cell line was similarly hypersensitive to killing by 3H2O at 37 degrees C as compared with early passage diploid hamster embryo cells. These results indicate that human cells are more radiosensitive than rodent cells when a radiation dose is protracted over several days rather than given as an "acute" exposure, and are consistent with the hypothesis that human cells are hypersensitive to low-dose-rate irradiation as compared with rodent cells.