The rat 13762 mammary carcinoma and the rat 9L gliosarcoma were grown subcutaneously in a hind limb of female, Fisher 344 rats. The oxygen content of the tumors was determined using an Eppendorf pO2 histograph. Fifty-to-sixty oxygen measurements were made per tumor and there were 8-to-10 animals per group. The percent of pO2 readings < or = 5 mmHg in the mammary carcinoma was 49%, this was decreased to 34% by administration of the hemoglobin preparation (8 ml/kg) and further decreased to 29% when carbogen (95% O2/5% CO2) breathing was added to administration of the hemoglobin preparation. The percent of pO2 readings < or = 5 mmHg in the gliosarcoma was 49%, this was decreased to 24% by administration of the hemoglobin preparation and further decreased to 0% when carbogen breathing was added to administration of the hemoglobin preparation. Therapeutic response was assessed over a single-dose range of radiation therapy (10, 20 and 30 Gray). The dose modifying factor produced by the hemoglobin preparation/air was 1.6 and by the hemoglobin preparation/carbogen was 2.7 in the rat 13762 mammary carcinoma. The dose modifying factor produced by the hemoglobin preparation/air was 1.9 and by the hemoglobin preparation/carbogen was 2.9 in the rat 9L gliosarcoma. Administration of a hemoglobin-based oxygen carrier reduced tumor hypoxia and increased tumor response to radiation therapy.