Brca2 deficiency is associated with chromosomal instability and an increased risk of breast and other cancers. To examine the effect of Brca2 deficiency on mutagenesis, we measured the spontaneous mutation rate at the endogenous hprt gene in the Brca2-deficient Chinese hamster cell mutant V-C8. A 4.3-fold increase was found in the spontaneous mutation rate at this locus, indicating the importance of Brca2 in the prevention of mutagenesis. In addition, following exposure to IR, a 2.3-fold increase in mutant frequency per Gy was found for V-C8 in comparison with wild-type V79. These data suggest a potential risk from ionizing radiation for BRCA2 patients.