The radiation response of logarithmic growth phase and fed plateau phase RIF-1 cells in vitro was found to be characterized by D0 (slope of cell survival curve on semilog plot) values of 110 and 133 rads and extrapolation numbers of 36 and 28, respectively. The response of the tumor in vivo to X-irradiation in nonanesthetized mice showed a dependence on the tumor implantation site. In the leg muscle, the response indicated that most cells were at an intermediate level of oxygenation, whereas in the subcutaneous tissue of the flank, the response of the tumor indicated that it had a small fraction (1.5%) of hypoxic cells of maximum radioresistance. Misonidazole radiosensitized the leg-implanted tumor as measured both by cell survival and regrowth delay. The median tumor cure dose of radiation in mice was 3,990 rads (3,670--4,340), which agreed closely with that predicted from the radiation survival curve. The tumor was relatively insensitive to a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea, sensitive to a single dose of cis-platinum, and highly sensitive to a single dose of cyclophosphamide.