Radiotherapy is administered with the assumption that all patients respond similarly to radiation although radiosensitivity does vary from patient to patient, resulting in different degrees of early and late effects. Because the dose given to a patient is limited by the response of normal tissue in the treatment field, it would be beneficial to determine the sensitivity of this normal tissue prior to therapy. Previous studies to predict radiosensitivity have used surviving fractions after a single dose given in vitro, however, differences in cell survival at this low level of kill are not easy to resolve. In this study, we set out to evaluate the use of alternative dose regimens which may better resolve differences in radiosensitivity. We have examined several radiation protocols for predictive value, including survival after high doses (6 Gy) at both high (112 cGy/min) and low (.882 cGy/min) dose rates and after fractionated doses of 2 Gy (6 fractions). A sensitive human fibroblast line (S11358) cultured from a patient showing severe effects after therapy is compared with a cell line (OMB1) cultured from an apparently normal subject. Differences between these cell lines have been compared with those between two human melanoma cell lines (SKMEL3 and HT144) which have shown resistant and sensitive response to radiation in vitro respectively. In both fibroblast and melanoma cell lines, the difference in the survival of normal and sensitive cells increased with increasing dose regardless of whether irradiation was delivered as low dose rate, high dose rate, or as fractionated doses. We propose that radiation doses which more closely mimic clinical treatment are more suitable than surviving fraction after 2 Gy (SF 2 ) for in vitro evaluation of relative radiosensitivities of cell populations.