Diuretic treatment (hydrochlorothiazide) induced a marked decrease of red cell membrane Na+K+ ATPase activity in excessive potassium loser hypertensive patients. The decreased activity occurred within 2-4 weeks of treatment and returned to baseline in 4-6 weeks after cessation of treatment. Simultaneously, red cell sodium increased, potassium decreased together with increased 24-h urinary excretion. The persistent low serum potassium may be due to impaired absorption of potassium from the gut as a result of suppressed enzyme activity since total body potassium appears also to decrease. The decreased Na+K+ ATPase activity may be due to a direct effect of the diuretic on cell membrane.