Attempts to correct tumor hypoxia with oxygen-carrying solutions have used high concentrations of inspired oxygen. Obtaining high levels of FiO2 using mask ventilation in older patients or in children may be difficult. When tested in mice bearing the Lewis lung tumor with 2, 3, or 4 Gy daily for 5 days, PBHS produced a dose-modifying factor (DMF) of 1.6 that was increased to 2.1 with carbogen (C). Studies using PBHS with X-rays demonstrated that daily administration of PBHS (12 ml/kg) 1 h before single X-ray fractions of 5, 10, 15, or 20 Gy with air resulted in a DMF of 1.6-1.7 in the FSaIIC tumor compared with radiation alone. Neither PBHS nor PBHS/(C) alone had any effect on tumor growth. The addition of PBHS (1.32 gm protein/kg) to treatment with melphalan (MEL) resulted in a 2.2-fold increase in the tumor growth delay (TGD) from 3 days to 7 days. Although C breathing (6 h) resulted in a small increase in TGD compared with MEL and air, the combination of PBHS with C (6 h) produced a 3.6-fold increase in TGD compared with MEL alone. The addition of PBHS to treatment with cyclophosphamide (CTX) resulted in a 2-fold increase in the TGD compared with CTX alone. However, the combination of PBHS and C was much more effective, resulting in a 4.6-fold increase in TGD to 16.5 days from 3.6 days for the drug alone. The TGD produced by cisplatin (CDDP) was less affected by the addition of PBHS to treatment. There was only a 1.3-fold increase in TGD with PBHS and CDDP compared with CDDP alone. The combination of PBHS and C was a more effective addition to CDDP, resulting in a 1.9-fold increase in TGD from 7.4 days to 14.1 days.