KORBELIK, M., PALCIC, B., AND SKARSGARD, L. D. Radiation-Enhanced Cytotoxicity of Misonidazole. Radiat. Res. 88, 343-353 (1981). The effect of ionizing radiation on the toxicity of misonidazole to hypoxic mammalian cells was examined. Cell toxicity response (log surviving fraction vs time of exposure to misonidazole in hypoxia) can be approximated by a biphasic curve: an initial period of approximately zeroslope shoulder, followed by exponential decrease in survival. Radiation reduced the zero-slope shoulder of toxicity response in a dose-dependent manner and at a given dose, the shoulder totally disappeared. The slope of the exponential region of the toxic response was unaffected. The same final survival level was achieved regardless of the sequence in which radiation and misonidazole exposure were applied to cells; in fact, there was no detectable repair of that radiation-induced damage which interacts with misonidazole toxicity (up to 24 hr). A mechanism for this interaction is proposed. Clinical implications are considered assuming that similar interaction between the two modalities takes place in vivo. Since the shoulder of toxic response is eliminated at high radiation doses, repeated administration of radiation and misonidazole could lead to additional kill of chronically and acutely hypoxic cells, if indeed both types are present in human tumors.