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The level of intracellular sodium concentration in hypertension is of theoretical interest. Using extensive in vitro manipulations, previous investigators have reported increased erythrocyte sodium content in human hypertension. In the present study, erythrocyte sodium (Nai) and potassium (Ki) concentrations were measured within seconds after venopuncture by centrifuging whole blood over oil to separate the erythrocytes from plasma. Labelled 125l-albumin and 57Co-EDTA were used to estimate plasma trapping. The presence of white cells and platelets in the cell pellets had no detectable effect on erythrocyte cation measurements. Twenty-eight white male hypertensives and 25 normotensive control subjects were studied. In hypertensive subjects, Nai was reduced and Ki was increased. Erythrocyte sodium and sodium: potassium ratio (Nai:Ki) of hypertensive subjects correlated inversely with their pressor responses to intravenous norepinephrine. The findings suggest increased erythrocyte Na, K-pump activity in human hypertension. Assuming that erythrocyte cation concentrations reflect those of vascular muscle, enhanced transmembrane sodium gradient does not preclude pressor hyper-responsiveness in hypertension.