Many mammals have the ability to autotransfuse a large quantity of red blood cells from the spleen into the active circulation during times of stress. This enhancement of the oxygen transport system has benefited the athletic mammal, that is, the thoroughbred horse, fox and greyhound in an improved aerobic performance. The role of the spleen in sequestering 50% of the total red cell volume in seals and horses, during times of inactivity, dramatically reduces the viscosity of the blood and therefore the work of the heart. In comparison, the human spleen contains only a small percentage of red blood cells, and has been primarily thought of as a lymphoid organ. The aim of this review is to emphasise the similarities between the human spleen and that of several athletic mammalian species during acute physiological stress. In the athletic mammalian model the expulsion of blood from the spleen is facilitated via the sympathetic nervous system resulting in contraction of smooth muscle within the splenic capsule. In comparison, the lack of smooth muscle contained within the human splenic capsule has meant that active contraction of the spleen has historically been viewed as unlikely, although evidence of contractile proteins within the red pulp have suggested otherwise. Exercise results in haemoconcentration, which has been attributed solely to a reduction in plasma volume. Indirect calculation of plasma volume changes utilise haemoglobin and haematocrit and assume that the circulating red cell volume remains constant. However, several studies have suggested that the human spleen could account for 30% of the increase in haematocrit. This would result in a substantial overestimation of the reduction in plasma volume, indicating that the expulsion of red blood cells from the spleen must not be overlooked when utilising these equations.