The presence of a circulating Na+ pump inhibitor has been assessed in 112 subjects by studying the effects of deproteinized plasma on ouabain binding to erythrocytes and/or inhibition of Na+-K+-ATPase activity. High levels of an inhibitor possessing some digitalis-like properties, were associated with essential hypertension, hypertensive heredity, treatment of hypertension with beta-blocking agents and high sodium intake. Low levels were found in hypertensives on diuretics, patients with chronic renal failure and normotensive controls. These observations are consistent with a possible role of this circulating inhibitor in the control of sodium balance and in hypertension.