The effects of X-irradiation on proliferating cells in the dentate subgranular zone were assessed in young adult Fisher 344 rats exposed to a range of X-ray doses and followed for up to 120 days. Apoptosis was quantified using morphology and end-labeling immunohistochemistry, and cell proliferation was detected using antibodies against the thymidine analog BrdU and the cyclin-dependent kinase p34(cdc2). Radiation-induced apoptosis occurred rapidly, with maximum morphological and end-labeling changes observed 3-6h after irradiation. Twenty-four hours after irradiation cell proliferation was significantly reduced relative to sham-irradiated controls. The number of apoptotic nuclei increased rapidly with radiation dose, reaching a plateau at about 3Gy. The maximum number of apoptotic nuclei was substantially higher than the number of proliferating cells, suggesting that non-proliferating as well as proliferating cells in the subgranular zone were sensitive to irradiation. Subgranular zone cell proliferation was significantly reduced relative to age-matched controls 120 days after doses of 5Gy or higher. These findings suggest that neural precursor cells of the dentate gyrus are very sensitive to irradiation and are not capable of repopulating the subgranular zone at least up to 120 days after irradiation. This may help explain, in part, how ionizing irradiation induces cognitive impairments in animals and humans.