A flow cytometric, anti-CD71-based method was used to measure peripheral blood reticulocyte and micronucleated reticulocyte frequencies in response to 137 Cs total body irradiation (TBI). In three independent experiments, groups of five female C57BL/6N mice were irradiated at graded doses up to 3Gy, and peripheral blood specimens were collected at 43h post-irradiation. Whereas the frequency of reticulocytes declined over the range of doses studied, micronucleated reticulocyte incidence was observed to increase in a dose-dependent manner up to 1Gy. At doses greater than approximately 1Gy, micronucleated reticulocyte frequencies declined with increasing exposure. These responses were highly reproducible, with significant effects on reticulocyte and micronucleated reticulocyte frequencies observed for the lowest dose studied (0.125Gy). A time-course experiment was performed to test whether radiation-induced cell cycle delay may explain saturation of the micronucleated reticulocyte endpoint at doses >1Gy. For this experiment, groups of four female C57BL/6N mice were exposed to 1, 1.5, or 2Gy TBI, and blood collection occurred at 12h intervals from 43 to 115h post-exposure. Reduced reticulocyte frequencies were observed for each dose studied, and the recovery of reticulocytes was increasingly delayed with higher radiation doses. Maximal micronucleated reticulocyte frequencies were observed at 43 or 55h, with progressively lower values at later time points. At no time did micronucleated reticulocyte frequencies induced by 1.5 or 2Gy significantly exceed that observed for 1Gy at 43h. These time-course data suggest that radiation-induced cell cycle delay cannot account for the micronucleated reticulocyte downturn phenomenon observed at doses greater than 1Gy. An alternate hypothesis is discussed whereby apoptotic elimination of severely damaged bone marrow erythroid precursors plays a dominant role in saturating the radiation-induced micronucleated reticulocyte response observed for C57BL/6N mice.