Oxygen carrying perfluorochemical emulsions have been shown to enhance the response of animal tumors to large single doses of radiation. Clinically, however, perfluorochemical emulsions are being used with only some fractions in multiple fraction radiation courses. To test the efficacy of a perfluorochemical emulsion under conditions that are closer to those used in current clinical trials, BA1112 rat sarcomas were treated with three fractions per week of 6 Gy per fraction. Once a week, animals were infused i.v. with a perfluorochemical emulsion at 15 ml/kg, and allowed to breathe carbogen (95% O2:5% CO2) for 30 minutes prior to and during irradiation. The 50% tumor control dose was 93.1 (87.9-103.1) Gy in the control arm compared to 74.3 (64.9-83.9) Gy for the animals given the perfluorochemical infusion plus carbogen breathing. The dose modification factor for intermittent perfluorochemical infusion and carbogen breathing was 1.26 (1.15-1.40). In a similar fractionated schedule, the hypoxic cell radiosensitizer, misonidazole, given once per week at 600 mg/kg, gave a dose modification factor of 1.22 (1.14-1.32).