Further investigation of a family with normaldosteronemic hyperpotassemia and low-renin hypertension showed 7 members from 3 generations, who ranged in age from 4-56 yr, to be affected. Results of earlier studies established a normally functioning renin-aldosterone system and normal renal handling of K+. Constant, albeit mild and asymptomatic, metabolic acidosis in all those affected prompted bicarbonate loading in both the propositus and his brother, which revealed a maximal renal tubular excretory capacity for bicarbonate reabsorption at serum levels of 18 mM/l and proved proximal renal tubular acidosis (PRTA). A linear increase in urinary fractional K+ excretion accompanied that of bicarbonate in both, as in normal individuals. Dextrose-insulin infusion in the brother failed to reduce hyperpotassemia. A generalized cell membrane defect that specifically impedes K+ influx (as opposed to an isolated renal tubular defect) underlies this autosomal dominant disorder.