Adult female prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) voles were compared to examine neural cell proliferation and the effects of estrogen manipulation on cell proliferation in the amygdala, ventromedial hypothalamus (VMH), and dentate gyrus of the hippocampus (DG). Unlike prior studies, our study focused on the amygdala and VMH, because they are involved in social behaviors and may underlie behavioral differences between the species. Meadow voles had a higher density of cells labeled with the cell proliferation marker 5-bromo-2′-deoxyuridine (BrdU) in the amygdala and DG than did prairie voles. Treatment with estradiol benzoate (EB) for 3 days increased the density of BrdU-labeled cells in the amygdala, particularly in the posterior cortical (pCorA) and medial (pMeA) nuclei, in meadow, but not prairie, voles. Furthermore, the majority of the BrdU-labeled cells in the pCorA and pMeA displayed either a neuronal or a glial progenitor phenotype, but no species or treatment differences were found in the percentage of neuronal or glial progenitor cells. To understand better estrogen's effects on adult neurogenesis, we also examined estrogen receptor-α (ERα) distribution. Meadow voles had more ERα-labeled cells in the pCorA and VMH, but not in the pMeA or DG, than did prairie voles. In addition, more than one-half of the BrdU-labeled cells in the amygdala of both species coexpressed ERα labeling. Together, these data indicate that estrogen alters cell proliferation in a species- and region-specific manner, and some of these effects may lie in the specific localization of estrogen receptors in the adult vole brain. J. Comp. Neurol. 489:166–179, 2005. © 2005 Wiley-Liss, Inc.