The objective of this study was to assess the pharmacokinetics of rhG-CSF after a single intraperitoneal injection 2 h post-TBI in B6D2F1 lethally irradiated mice and to analyze the effect of rhG-CSF on the endogenous response of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in these animals. For comparison, these cytokine serum levels have also been measured in nonirradiated mice. The serum concentrations of rhG-CSF in irradiated mice were higher than in nonirradiated mice at all time points during the first 60 min after injection. Furthermore, rhG-CSF administration failed to induce detectable endogenous serum levels of IL-3, IL-6 and GM-CSF, at least in the 72-hour period after administration of the rhG-CSF. The radioprotective effect of rhG-CSF in lethally irradiated mice is not mediated by an increase in endogenous serum levels of these three cytokines.