Neural stem cells in the adult brain may contribute to learning and neural plasticity, to stress-induced neuropathologic changes, to mood and affective disorders, and to other complex brain functions. Learning, an enriched environment, and exercise (as modeled by running) all increase neural stem cell proliferation in the hippocampus and improve performance on learning tests, whereas acute ethanol consumption decreases neural stem cell proliferation in the hippocampus. To explore the interaction of exercise and ethanol consumption (two behaviors important for mental health), C57BL/6 mice were given access to ethanol, a running wheel, or both, and neural stem cell proliferation was investigated in the hippocampal dentate gyrus, corpus callosum, and forebrain subventricular zone of these mice. Mice given access to ethanol consumed large amounts of ethanol, and mice given access to a running wheel ran long distances, with the combined groups' behavior being comparable to that of the ethanol access alone group and of the running wheel access alone group. Neural stem cell proliferation was assessed by treating mice with bromodeoxyuridine (12 days, 300 mg/kg/day, i.p.) and evaluating consequent immunoreactivity. Exercise increased bromodeoxyuridine immunoreactivity in dentate gyrus, but not in other brain regions studied. Self-administration of ethanol decreased bromodeoxyuridine immunoreactivity by approximately 60% (P < .01) in dentate gyrus; 70% (P < .001), in forebrain; and 80% (P < .001), in corpus callosum. Findings for exercise and ethanol consumption combined were remarkably similar to those for exercise alone. The opposing effects of ethanol consumption and exercise on neurogenesis could contribute to the CNS pathology and health benefits, respectively, of these two behaviors.