Data from both cross-sectional and longitudinal studies provide compelling evidence that circulating blood volume can be influenced by regular physical activity or inactivity. Expansion or contraction of plasma volume can account for most of the alteration in circulating blood volume during the initial 1 to 2 weeks of changing physical activity patterns; after this time, altered blood volume may be distributed equally between plasma and red cell volumes. Alterations in circulating blood volume that accompany changes in physical activity represent a net change in total body water and solutes that are associated with increased or decreased water intake and urine volume and solute output. The mechanism of altered urine output appears to be a modified renal tubular reabsorption of sodium. The expansion of blood volume that accompanies physical activity provides advantages of greater body fluid for heat dissipation (sweating) and thermoregulatory stability as well as larger vascular volume for greater cardiac filling and stroke volume and cardiovascular stability during exercise and orthostatic challenges. The opposite is true when blood volume is reduced during periods of relative physical inactivity. The observation that underlying mechanisms for alteration in blood volume with physical activity and inactivity are similar but respond directly opposite suggests that they are intricately related. These relations have implications as to a mechanism by which physical activity and fitness may be protective against reduced blood volume and subsequent development of cardiovascular disease associated with aging.