The effects of a 2-litre isotonic saline infusion, with and without prior oral canrenone (150 mg) administration, on erythrocyte Na+, K+ pump, urinary sodium excretion and arterial pressure were evaluated in nine patients with essential hypertension. Ouabain-sensitive Na+ efflux in fresh erythrocytes was used as an index of Na+, K+ pump activity, and the inhibitory effect on this ion efflux of preincubation of erythrocytes in plasma was used to test the presence of a circulating ouabain-like substance. Erythrocyte Na+, K+ pump activity decreased significantly (P less than 0.01) after saline infusion; canrenone administration was able to prevent this inhibition. Plasma from hypertensive patients obtained before saline infusion significantly (P less than 0.01) inhibited the Na+, K+ pump of erythrocytes from normal subjects, while plasma taken after the saline infusion plus canrenone was unable to produce any significant inhibition. Both systolic and diastolic arterial pressure fell significantly (P less than 0.05) only at the end of saline infusion with prior canrenone administration. This study supports the hypothesis that protection of Na+, K+ pump against endogenous inhibitors, other than exogenous, seems to be a pharmacological effect of canrenone, and may partly explain its antihypertensive activity.