PURPOSE: We investigated the effects of fractionated radiation treatments on the life spans of athymic rats bearing intracerebral brain tumors. METHODS AND MATERIALS: U-251 MG or U-87 MG human glioblastoma cells were implanted into the brains of athymic rats, and the resulting tumors were irradiated once daily with various doses of ionizing radiation for 5 consecutive days or for 10 days with a 2-day break after Day 5. RESULTS: Five daily doses of 1 and 1.5 Gy, and 10 doses of 0.75 and 1 Gy, cured some U-251 MG tumors. However, five daily doses of 0.5 Gy increased the survival time of animals bearing U-251 MG tumors 5 days without curing any animals of their tumors. Ten doses of 0.3 Gy given over 2 weeks extended the lifespan of the host animals 9 days without curing any animals. For U-87 MG tumors, 5 daily doses of 3 Gy produced an increased lifespan of 8 days without curing any animals, and 10 doses of 1 Gy prolonged lifespan 5.5 days without curing any animals. The differences in extension of life span between the 5- and 10-fraction protocols were minor for either tumor type. CONCLUSION: The finding that the U-251 MG tumors are more sensitive than U-87 MG tumors, despite the fact that U-251 MG tumors contain many more hypoxic cells than U-87 MG tumors, suggests the intrinsic cellular radiosensitivities of these cell lines are more important than hypoxia in determining their in vivo radiosensitivities.