Alterations in cellular calcium metabolism are presumed to be the basis of the vasoconstrictive process that sustains elevations in arterial pressure. Altered membrane sodium transport can effect changes in intracellular free calcium concentration through changes in transmembrane sodium gradients and membrane depolarization. Thus, changes in membrane sodium transport could produce calcium accumulation in vascular smooth muscle, resulting in vasoconstriction and arterial hypertension. Multiple sodium transport abnormalities exist in tissues of genetically hypertensive rats, and blood cells of human essential hypertensives. Na+-K+ cotransport and Na+-Li+ countertransport abnormalities appear to be primary membrane defects, but a direct physiologic link of these to vasoconstriction remains to be established. Evidence for circulating Na,K-ATPase inhibitors in hypertension is now widely reported, and Na,K-ATPase inhibition provides a rationale for vasoconstriction through altered calcium and/or neurotransmitter metabolism. Na,K-ATPase inhibition in hypertensive disease appears to arise not as a primary abnormality in membrane transport, nor as a phenomenon secondary to hypertension per se, but as a physiological response to compensate for excess extracellular fluid volume accumulation.