The effects of sodium depletion of plasma norepinephrine (NE) kinetics were studied in 14 patients with essential hypertension using the steady state NE infusion technique on the theoretical basis of a two-compartmental open model. The calculated half time of rapid removal phase (t1/2α) of plasma NE was significantly delayed in the hypertensives (1.20 ± 0.22 min, mean ± SD) than in normal subjects (0.89 ± 0.14) (p < 0.01). The total clearance rates were comparable between the 2 groups (47 ± 7 vs 48 ± 11 ml/kg/min). The rates of the endogenous NE outflow into the circulation (RE-NE) were not significantly different between normal (5.29 ± 1.68 ng/kg/min) and hypertensives (7.69 ± 5.42), although 5 hypertensive patients (36%) showed an increased RE-NE above the normal range. the prolonged half time (t1/2α) in the hypertensives tended to be shortened after sodium depletion induced by either low sodium diet or diuretics (1.04 ± 0.22, p < 0.001). Both plasma NE and RE-NE were significantly increased after sodium depletion. A close correlation was observed between plasma NE and RE-NE (r= 0.907, p < 0.001) in these subjects. These results suggest the slowed neuronal uptake of NE at the sympathetic nerve terminals in some patients with essential hypertension occurring in part as a sodium-mediated consequence.