Response modifiers have been defined and several examples of modification of response of tissues of laboratory animals or of theoretical models were presented. I have reviewed several efforts to assess the clinical value of serveral of the radiation response modifiers and described some major problems. A major and quantitatively undefined problem for clinical testing of response modifiers is the heterogeneity of clinical material. An area of laboratory and clinical investigation which has large potential is examination for indicators of response probability so as to identify individual patients who are likely to benefit by application of particular radiation response modifiers. There is a need for clinical trials to determine if the results of Henk and associates can be verified. Had Henk been able to publish such results in 1962 instead of 1977, it is virtually certain there would have been considerable effort to verify his results and to investigate numerous other sites. Further, there would have been greater stimulus to the laboratory to provide means to stratify patients according to evidence of hypoxic regions or failure to reoxygenate. Also efforts would have been made to increase the efficacy of hyperbaric oxygen, e.g., suppression of oxygen utilization. The disappointing results from studies with misonidazole should not discourage the testing of new sensitizers of hypoxic cells provided they can be administered at drug doses which achieve substantially higher ER values. New trials of the pyrimidine analogs against tumor which are surrounded by slowly or non-dividing normal tissue appear appropriate. Emphasis was placed on the practical clinical value of radiation protectors which can be applied topically or administered regionally.