Effective population size (Ne) is a fundamental concept that links population structure to the evolutionary processes that shape genetic variation. Demographic estimates of Ne may be influenced by a number of factors, including adult sex ratio and variance in individual reproductive success. Genetic estimates of Ne are influenced not only by these variables but also by neighborhood size, degree of population substructure, and historical changes in population size. Hence, comparisons of demographic and genetic estimates of Ne may yield important insights into the parameters that determine effective size. To explore interactions between demography and Ne, we compared estimates of effective population size/census size (Ne/N) for 2 demographically distinct populations of the talar tuco-tuco (Ctenomys talarum), a subterranean rodent from Buenos Aires Province, Argentina. Examination of data on adult sex ratios and reproductive success obtained from long-term field studies of C. talarum at Mar de Cobo and Necochea led us to predict that Ne/N should be smaller for Mar de Cobo. Demographic and genetic estimates of Ne/N were consistent with this prediction. However, interpopulation variation in Ne/N was greater for the genetic data set. Based on analyses of microsatellite variation, we suggest that this result is due primarily to differences in current demography, rather than historical reductions in population size. The observed differences in Ne/N imply that the strength of genetic drift differs between Mar de Cobo and Necochea, thereby potentially affecting patterns and rates of diversification among populations of C. talarum.