The present study was conducted in 15 essential hypertensives to evaluate the modifications of plasma levels of an endogenous Na/K ATPase inhibitor, blood pressure, forearm hemodynamics and plasma renin activity (PRA) elicited by an intravenous saline infusion (0.9% NaCl at the mean rate of 0.22 mL/min/kg body weight for 2 h). The response to saline was determined in the whole hypertensive population as well as in two subgroups of patients classified according to their rate of PRA suppression in response to volume expansion by comparison with normotensive controls (Normal- and Low-suppressors: N-S, L-S). Over the whole group of hypertensive patients, NaCl load provoked an increase in Na/K ATPase inhibitory activity, measured by enzyme-coupled assay, which was linearly related to PRA decline (r = 0.73) and to the increase in mean blood pressure (r = 0.57). These effects were clearly enhanced by considering L-S patients alone. Urinary Na/K ratio after saline infusion was significantly higher in L-S as result of a lesser potassium excretion in this subgroup. Our results support the hypothesis that acute volume expansion with saline causes an increase in plasma levels of an endogenous sodium pump inhibitor with hemodynamic effects and whose release is related to the individual handling of infused fluids and to the degree of renin-angiotensin-aldosterone suppression.