Mechanical integration of the cardiac, muscular and ventilatory pumps enables mammals to vary cardiac output over a wide range to match metabolic demands. We have found this integration lacking in a lizard (Iguana iguana) that differs from mammals because blood flow from the caudal body and ventilation are maximal after, rather than during, exercise. Because Iguana iguana are constrained from ventilation during intense locomotion, they appear to be unable to recruit the abdomen and thorax as a pump for venous return. This constraint on simultaneous running and costal breathing arises from their musculoskeletal design, which is similar to that of basal tetrapods, and so a constraint on venous return during exercise may be ancestral for tetrapods. We suggest that mechanical coupling of the pulmonary and cardiac pumps may have been important for the evolution of high-speed locomotor stamina in terrestrial vertebrates.