IN PREVIOUS experiments on the development and transplantation of locally radioresistant mouse lymphoma, the larger tumors, previously treated or untreated, appeared to be the more resistant to the effects of local irradiation. This phenomenon was observed in two lines of lymphoma cells in two strains of mice and seem to agree with Sturgis' clinical observation (9) that in leukemia in man acquired radioresistance is related to progression of the disease. It has also been observed in human subjects with Hodgkin's disease that relatively large tumors require larger doses of irradiation for local eradication (7). To test whether this observation is statistically significant, it was decided to treat groups of mice with tumors of various sizes (0.8 to 2.2 em. in diameter) with single doses of 200 to 1,000 r. Method For these experiments, the Gardner line of lymphosarcoma was transplanted subcutaneously into the right flank of CBA mice. This tumor has been found to grow equally well in the parent C3H mice in which it arose and in the CBA strain (4). For transplanting, the tumor tissue was dissected out immediately after the animal had been sacrificed by fracturing the cervical spine. The tumor cells were suspended in sterile 0.85 per cent sodium chloride solution, a random cell count being 32,000 cells per cubic milliliter. Usually 0.02 to 0.04 ml. produced a visible wheal in the mouse flank, and this was considered a satisfactory transplant. For local irradiation, the untreated portion of the mouse was shielded with 2.0 rnrn. of lead, which absorbs over 98 per cent of the radiation employed. Technical factors were: 140 kvp, 30 em. targetskin distance, 15 rna, and 2.0 mm. Al filter (h.v.I. 4.2 mm. AI). With these factors, slightly over 21 r in air are delivered to the surface of the skin for each minute of irradiation. The tests were carried out in a large number of transplant generations extending over a period of two years. In the earlier generations the tumor was less virulent; it grew locally to a large size, but at autopsy the majority of the mice revealed no evidence of dissemination. The tumors in these animals often grew to 3 or 4 em. in diameter. In later transplant generations, metastasis occurred much more frequently, often before the tumor attained a diameter of 2.0 em. This increasing virulence with serial transplantation was also detected in the response to irradiation, in that the tumors of 1.0 em. in diameter, or smaller, were more resistant to small doses of local irradiation in the 200 to 400 r range. Results In measuring the response to irradiation, the end-point selected was survival of the host with no evidence of tumor two months after irradiation. These mice were considered cured.