Vascular wall shear stress must be within the physiologic range for normal blood flow, including preferential flow patterns and the maintenance of the antithrombotic phenotype of the endothelium. Wall shear stress varies with blood viscosity. The hematocrit, i.e., the volume percent of blood comprised of erythrocytes, is a strong determinant of blood viscosity, wall shear stress, cardiac work and oxygen transport. We hypothesize that in humans the hematocrit is modulated to maintain constant wall shear stress in the carotid sinus, a dilatation of the internal carotid artery that is tailored to detect wall shear stress. These data modulate the renin-angiotensin-aldosterone system, including the concentration of erythropoietin, the hormone that controls erythrocyte production. Using previously published data, we show that the different blood viscosities and carotid diameters in the sexes combine so that wall shear stress is virtually identical in both. Maintaining normal wall shear stress may explain the increasing hematocrit with growth and sports anemia, a mild dilutional anemia in some exceptionally fit athletes. Previously, these phenomena were poorly understood because of the assumption that the hematocrit is determined by the need to maximize oxygen transport. We term this the “reductionist” view. This view was reinforced historically by overestimation of tissue oxygen needs. Identification of additional complexity makes a holistic approach, examining an entire system rather than its parts, more attractive. The authors argue that a holistic approach is necessary for understanding what determines the hematocrit, explaining the sex difference in hematocrit, the increasing hematocrit with growth, and sports anemia.