The objective of the proposed research is to extend our knowledge and understanding of the role of hypoxic cell radiosensitizers for radiotherapy. The studies will involve transplantable murine tumors, using local tumor control (TCD50) as an end point for evaluating tumor response. Normal tissue response will be evaluated using leg contraction as an end point. This technique has the advantages of being simple to use, a measure of late response, and dose-responsive in the range of commonly obtained TCD50 values including those obtained with hypoxic cell sensitizers. Four main subdivisions are: 1) Completion of studies determining optimal fractionation schedules for the C3H mouse mammary carcinoma MDAH-MCa-4 using misonidazole. Extension of these studies to two other tumor lines. 2) Comparison of time-dose relationships for acute skin response, skin contraction, and leg contraction in order to determine the predictive value of the early reactions for late responses. 3) Evaluation of the therapeutic potential of misonidazole plus hyperthermia in combination with radiotherapy. 4) Screening a limited number of new sensitizers in vivo which have passed the preliminary screening procedures established by the Radiosensitizer/Radioprotector Subcommittee.