The effect of Fluosol DA 20%, an emulsion of perfluorochemicals, in combination with carbogen (95% O2 and 5% CO2) breathing on the response of mouse tumors to radiation was studied. When A/J mice bearing SCK tumors in the right hind limb were injected iv with Fluosol DA 20% at 12 ml/kg and exposed to carbogen for 1 h before and during the irradiation of tumors, the response of tumors to a single dose of X irradiation was significantly enhanced. The dose modification factors for growth delay and cure of SCK tumors were 2.10 +/- 0.01 (SE) and 1.86 +/- 0.18 (SE), respectively. Such a treatment slightly increased the radiation-induced skin damage by a factor of 1.17 +/- 0.02 (SE), resulting in a therapeutic gain of 1.79 +/- 0.01 (SE) for the growth delay and 1.59 +/- 0.09 (SE) for the curability. Carbogen breathing alone also increased the response of tumor and skin to radiation, but it was far less effective than the combination of Fluosol DA 20% and carbogen breathing. It was concluded that iv injection of Fluosol DA 20% in conjunction with carbogen breathing significantly increased the O2 transport to hypoxic areas in the SCK tumors and thus significantly enhanced the tumoricidal effect of radiation on SCK tumors.