SUMMARY Sixteen patients with refractory hypertension were submitted to rigorous sodium depletion while cardloTascular bomeostasis was monitored with measurements of hormonal and bemodynamlc parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r « 0.70,p< 0.005). Blood pressure (BP) decreased from 176/116 ± 8/3 to 155/109 ± 6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r= 0.68,p< 0.05) and a dose negative correlation between percent increase in PRA and the ratio of fall in mean Mood pressure (MAP), per unit of weight loss (r= −0.73,p< 0.005). Thns, patients with the least percent increase In PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be tne factor limiting antihypertenslve efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.