Reports of altered sodium transport in the red blood cells of individuals with essential hypertension and their offspring stimulated interest in this hypothesis. Several proposals were offered to explain how alterations in sodium transport similar to those observed in red blood cells could lead to elevated blood pressure when present in the renal tubules or vascular smooth muscle. Studies of the sodium-lithium countertransport system indicated that red blood cell sodium transport pathways may provide informative phenotypes that relate blood pressure and essential hypertension more closely with genetic factors.