In this study, we investigated the response of irradiated bone marrow cells to granulocyte colony-stimulating factor (G-CSF). Freshly harvested bone marrow cells were treated with either saline (vehicle control) or 20 ng/ml of G-CSF. Thereafter, cells were separated into nonirradiated (no-IR) and irradiated (IR, 0.5 Gy) groups. IR cells exhibited a higher proliferation rate in response to G-CSF, as compared to the no-IR cells. Reduced levels of reactive oxygen species indicated that G-CSF-treated IR cells produced fewer free radicals, as compared to the no-IR cells. The G-CSF-treated IR cells also had a lower apoptotic rate than their no-IR counterparts. Furthermore, G-CSF-treated IR cells exhibited less alteration of mitochondrial membrane potential, as compared to the no-IR cells. Finally, the mitochondrial number increased in the G-CSF-treated IR cells. The radiation-induced increase in plasma IL-6 in vivo could be enhanced by the administration of G-CSF. The data suggest that radiation potentiates the response of bone marrow cells to G-CSF treatment.