Age-dependent epithelial cell hyperplasia in the dorsal and lateral lobes of Brown Norway rats is analogous to benign prostatic hyperplasia in aging men. A major question is whether differential lobe-specific and age-dependent proliferation of cells, rather than cell survival, contributes to the hyperplasia. Although serum testosterone levels decline in aged rats, active cell proliferation was detected as Ki67-positive cells in the dorsal and lateral lobes. We determined whether androgens differentially affect cell proliferation and cell-cycle regulatory proteins in the prostate lobes of young and aged rats. Castrated rats were treated with different doses of testosterone to restore serum levels to those of intact young or aged rats. Rates of cell proliferation, measured by BrdU-labeling, peaked after 3 days of testosterone treatment in all lobes. BrdU-labeling indices were higher in the dorsal and lateral lobes of aged than of young rats with equivalent serum testosterone levels. No age-dependent difference was seen in the ventral lobe. Cell proliferation was marked by increased levels of cyclins D1 and E and cyclin-dependent kinases 4 and 6, decreased p27 and increased phosphorylation of Rb. Levels of cyclins D1 and E were higher in the dorsal and lateral lobes of intact and testosterone-treated aged than young rats. Confocal immunofluorescent microscopy documented changes in cdk4 and cyclin D1 subcellular localization. Cyclin D1 nuclear localization correlated with the timeframe for cell proliferation. In conclusion, rates of cell proliferation and levels of cell-cycle regulatory proteins that control the G1/S transition exhibit lobe-specific and age-dependent differences in response to androgens.