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Since the terrorist attack of September 11, 2001, preparation by the health care system for an act of terrorism has been mandated by leaders of governments. Scenarios for terrorist acts involving radioactive material have been identified, and approaches to management (based on past experience from atomic weapons detonations and radiation accidents) have been developed. Because of their experience in managing patients with profound cytopenia and/or marrow aplasia, hematologists will be asked to play a significant role in evaluating and treating victims of mass accidental or deliberate exposure to radiation. This review provides a framework for understanding how radiation levels are quantified, how radiation alters the function of hematopoietic (and nonhematopoietic) cells and tissues, and how victims receiving a significant radiation dose can be identified and managed. In Section I, Dr. Nicholas Dainiak reviews four components of the Acute Radiation Syndrome: the hematopoietic, neurovascular, gastrointestinal and cutaneous subsyndromes. Clinical signs and symptoms are discussed for exposed individuals at the time of initial presentation (the prodromal phase) and during their course of disease (the manifest illness). In Section II, he presents clinical and laboratory methods to assess radiation doses, including time to onset and severity of vomiting, rate of decline in absolute blood lymphocyte count and the appearance of chromosome aberrations such as dicentrics and ring forms. Potential scenarios of a radiation terrorist event are reviewed, and methods for initial clinical assessment, triage, and early management of the acute radiation syndrome and its component subsyndromes are summarized. In Section III, Dr. Jamie Waselenko reviews the hematopoietic syndrome, and presents guidelines for the use of cytokine therapy, antibiotics, and supportive care that have been developed by the Strategic National Pharmaceutical Stockpile Working Group. Results of preclinical and clinical growth factor therapy studies with G-CSF, GM-CSF, pegylated G-CSF, SCF, and IL-3 are summarized. When and how potassium iodide should be used after exposure to radioiodines is also reviewed. In Section IV, Dr. James Armitage describes a narrow "window" of 7 to 10 Gy where therapy with stem cell transplantation may be appropriate. Victims who are candidates for allotransplantation should not have major trauma or significant injury to other (nonhematopoietic) tissues. Rarely, victims may have an identical sibling or autologous stored marrow or blood stem cells, in which case the threshold for transplantation is 4 Gy. In Section V, Dr. Thomas MacVittie describes new directions for therapy, using cytokines such as IL-7, keratinocyte growth factor, and FLT-3. The potential for combinations of cytokines to enhance hematopoietic recovery is also reviewed.