Physical exercise is a robust stimulus that enhances hippocampal neurogenesis via cell proliferation in rodents. We examined the role of systemic angiotensin (Ang) peptides in exercise-dependent enhancement of neurogenesis in the adult rat hippocampus. Plasma angiotensin peptide concentration increased rapidly in response to 30 min of treadmill exercise. After undertaking this exercise once daily for a week, the number of proliferating cells in the hippocampus, identified by 5-bromo-2'-deoxyuridine (BrdU) incorporation, had increased compared with controls. To mimic the increase in plasma Ang peptide concentrations brought about by exercise, rats were injected with 10(-5)M Ang II once daily for a week. The number of BrdU-incorporating cells and of doublecortin (DCX)-expressing immature neurons in the hippocampus rose approximately 1.5 and 1.9-fold compared with controls, respectively. The effects were completely abolished by an Ang II receptor subtype 1 antagonist losartan. These findings, taken together, suggest that an increased concentrations of Ang peptides in the systemic circulation during exercise may promote neurogenesis in the adult rat hippocampus.