Ionizing radiation is a complete carcinogen,able both to initiate and promote neoplastic progressionand is a known carcinogen of human and murine mammarygland. Tissue response to radiation is a composite of genetic damage, cell death and induction ofnew gene expression patterns. Although DNA damage isbelieved to initiate carcinogenesis, the contribution ofthese other aspects of radiation response are beginning to be explored. Our studiesdemonstrate that radiation elicits rapid and persistentglobal alterations in the mammary glandmicroenvironment. We postulate that radiation-inducedmicroenvironments may affect epithelial cells neoplastictransformation by altering their number orsusceptibility. Alternatively, radiation inducedmicroenvironments may exert a selective force oninitiated cells and/or be conducive to progression. A key impetus forthese studies is the possibility that blocking theseevents could be a strategy to interrupt neoplasticprogression.