Neurogenesis continues throughout adulthood in mouse dentate gyrus, and is influenced by environmental, endocrine, and pharmacological conditions. Although running wheel exercises have been reported to enhance neurogenesis, the effects on neuronal death in dentate gyrus are not well understood. The precise control of the production and elimination of neurons is thought to be important for the maintenance of a relatively constant number of neurons in the adult nervous system and for the regulation of adult brain function. We report here that running wheel exercises enhance the death of pre-existing neurons as well as neurogenesis in dentate gyrus. In addition, we analyzed mice lacking an NMDA receptor varepsilon1 subunit, and found that the enhancement of the neuronal death by the exercises is suppressed in the varepsilon1 subunit knockout mice. These results suggest that running wheel exercises accelerate neuronal turnover in mouse dentate gyrus, through the activation of NMDA receptors.