Purpose To determine the effects of total body irradiation (TBI) dose, fractionation, and lung shielding on hematopoietic stem cell homing to the bone marrow. Material and Methods Bone marrow (BM) cells were extracted from tibiae and femurs of B6-GFP mice and were transplanted into B6 mice. Recipient mice had either: 1) no radiation, 2) single dose TBI at 13.6 Gray (Gy), 3) single dose TBI at 13.6 Gy with reduced lung exposure to 0.4 Gy by shielding, 4) split dose TBI at 12 Gy to twice/day over four days, or 5) split dose TBI at 12 Gy to twice/day over four days with reduced lung exposure to 0.36 Gy by shielding. The last radiation exposure preceded tail vein injection by 4–6 hours. Mice were sacrificed after 18 hours. Results Homing of GFP positive, lineage negative cells was not significantly improved in any irradiated group compared to control. Homing of GFP positive, lineage negative, Kit positive cells was significantly worse in all irradiated groups. Conclusion TBI does not improve the homing of lineage negative donor BM cells to the recipient marrow. Homing of lineage negative, Kit positive donor BM cells was significantly worse following TBI, with or without lung dose reduction.