We propose to investigate the radiobiology of accelerated heavy ions and to perform pre-therapeutic studies as part of a program of full-scale studies on heavy ion uses in biology and medicine, in particular, therapy of tumors. The major source of heavy ions is the Berkeley Bevatron and its modified form, the Bevalac. The Bevalac will be a facility capable, when completed, of producing accelerated beams of various atomic nuclei up to atomic number of about Z equals 26. The particle energies will be variable up to 2.5 BeV/nucleon, and intensities will be ample for all contemplated radiobiologic and therapeutic applications. This interdisciplinary effort forms part of a larger effort at Lawrence Berkeley Lab. in the science of heavy ion beams. The accelerators are National facilities available for qualified users: A. Molecular and cellular radiobiology of normal and cancer cells - The effects of various heavy particles will be evaluated in tissue culture with respect to oxygen effect, relative biological effectiveness, molecular nature of radiolesions, repair and radiosensitivity during cell division cycle. B. Acute responses of mammalian tissues to heavy ions - Quantitative studies of the effects of heavy ion beams on normal tissues including skin and intestinal epithelium, lung, hemopoietic tissues, kidneys, liver, bone endocrine tissues and nerve tissue. Single and protracted doses will be given. C. Chronic responses of mammalian tissues to heavy ions, including carcinogenesis - Late radionecrosis, scar tissue formation, carcinogenesis, leukemogenesis and longevity will be evaluated in mice following single and protracted doses of heavy ions. D. Tumor radiobiology, including cellular kinetics of selected animals - Cell turnover kinetics and other factors of tumor-host response will be evaluated in appropriate rodent tumor test systems. E. Preparations for human radiotherapy - Beam localization and delivery techniques and dose schedules for human radiotherapy will be improved from existing methods based on information in cellular and animal test systems.