The objectives of this project are to demonstrate that properly fractionated total body irradiation can sterilize advanced lymphomas in mice, and to elucidate the variables in such a system. It has been demonstrated that lymphoma localized in the region of the thymus gland may be sterilized by upper thoracic irradiation. The dose needed is above the total body LD50/30 for mice. The limiting factor at such dose levels is damage to the bone marrow. Survival curves performed on mouse marrow yield a straight dose-log survival curve after an initial shoulder. Recovery experiments indicate a complex recovery pattern with a maximum at about 4 to 6 hours. Previous experiments have demonstrated that repeated small doses of irradiation continue to demonstrate a similar recovery pattern with a maximum recovery at 4 hours. In contrast, there is some evidence that lymphomas arising in the thymus or early transplantation passages of such lymphomas have dose-log survival curves which are linear. Radiation fractionated every 4 hours would thus be expected to have the same effect as acute irradiation on the lymphoma cells while allowing for recovery after each fraction in the bone marrow. Calculations indicate that such fractionation should eradicate the lymphoma while allowing adequate bone marrow survival compatible with the life of the animal. Further demonstration of the linearity of the lymphoma dose-log survival curve will be necessary. These data will be used to predict the fractionation schemes necessary to achieve sterilization of the lymphoma while allowing survival of the mice. In addition, combined chemotherapeutic-irradiation approaches are being investigated. Initial experiments will involve cyclophosphamide and steriods.