Individuals who inherit one defective copy of the BRCA2 gene are at a risk of developing breast cancer. Conditional inactivation of Brca2 within mouse small intestinal epithelium previously has been shown to lead to increased al levels of spontaneous and DNA damage-induced cell death. In this issue, Hay et al. have used this model system to demonstrate an exquisite sensitivity of non-neoplastic Brca2-deficent cells to a potent inhibitor of Poly(ADP-ribose) polymerase-1 (PARP-1). Very high levels of epithelial cell apoptosis were accompanied by rapid depletion of Brca2⁺ cells (stained blue) following repeated doses of the inhibitor (lower panel) compared to untreated (uppper panel). In light of previous studies, which suggest PARP inhibition as a potential therapy against BRCA2⁺ tumours, the data presented here on physiologically normal Brca2-deficient cells support its additional use as a prophylactic therapy in individuals harbouring the BRCA2 mutation. Work is underway to test this hypothesis in mice bearing defective Brca2 within mammary epithelium. For details, see article by Hay et al. on page 10145 of this issue.