To establish a basis for a possible strategy for bone marrow ablation or therapy, we examined the effect of bromodeoxyuridine (BrdU) incorporation into DNA on the genotoxic and cytotoxic effects of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) in normoblasts in vivo. Cytotoxicity and genotoxicity were established by time–response curves of polychromatic erythrocyte (PCE) and micronucleated polychromatic erythrocyte (MN-PCE) frequencies, respectively, in mouse peripheral blood samples. The group treated with 153Sm-EDTMP showed a clear induction of MN-PCEs; however, the group treated with BrdU plus 153Sm-EDTMP paradoxically showed only a slight increase with respect to untreated controls. Treatment with 53Sm-EDTMP caused a small reduction in PCE frequency, but exposure to BrdU or to BrdU plus 53Sm-EDTMP reduced the PCE frequency significantly from 32 h to the end of the experiment. The PCE frequencies in the BrdU plus 53Sm-EDTMP group were significantly lower than in the BrdU control group at the final time and were much lower than the group treated with only 53Sm-EDTMP, which returned to basal values. The results suggest the radioinduction of a lethal lesion in BrdU-substituted DNA that cannot be repaired easily and does not permit cell division and micronucleus formation.