The mammalian RAD51 gene is a homologue of the yeast RAD51 and E. coli RecA genes, which are involved in recombination and DNA repair. We examined the role of RAD51 protein in mouse cells using RAD51 antisense phosphorothioate oligonucleotides (ODNs). The extraluminal delivery of 50 nM or 100 nM of antisense ODNs with lipofection to mouse cells resulted 90% suppression of RAD51 protein expression. The antisense ODNs significantly inhibited the cell growth and the treated cells became more sensitive to gamma-irradiation than the control groups. These results indicate mouse RAD51 plays an essential role in cell proliferation and radioresistant activity.