Tumor cell survival characteristics were assessed following 60Co gamma-irradiation of the Lewis lung carcinoma as 500-cu mm s.c. tumors or as 0.5-cu mm (1 mm in diameter) pulmonary metastases. Cells in the small pulmonary tumors were markedly more radiosensitive (D0 = 106 rads; hypoxic fraction less than 0.005) than were those in large s.c. tumors (final D0, 315 rads; hypoxic fraction, 0.36). When pulmonary metastases were excised and irradiated intact under well-oxygenated conditions in vitro, the hypoxic fraction rose to 0.30. This implies that, under normal in situ conditions, these nodules contain a microvascular system that achieves adequate oxygen supply to the great majority of tumor cells. Thus, the tumor cells within these small metastatic implants were more sensitive to irradiation, largely due to better oxygenation, and may be more sensitive to chemotherapy, due to better drug availability.