In the adult hippocampus, neurogenesis is influenced both by external stimuli, such as physical exercise, and by intrinsic conditions like age and disease. However, the way in which many of these external and internal cues interact in this process remains poorly understood. We have used a new, more precise, stereological cell counting method that involves confocal microscopy to analyze the effects of exercise on adult neurogenesis in the mouse. We found that treadmill exercise increases the number of differentiating neurons (doublecortin/calretinin cells) in the granule cell layer of the mouse hippocampus in a manner that is directly related to the size of the mature granule cell population. More immature neurons were found after exercise in animals that had a larger dentate gyrus (DG), while no changes were observed in those with a smaller DG. This differential response to physical exercise suggests that the pre-existing neuronal population regulates the neurogenic response in the DG to external stimuli. These data raise the possibility of anticipating an individuals' response to therapeutic interventions (like exercise) aimed at augmenting dentate neurogenesis and alleviating or preventing cognitive decline.