Further investigation of a family with normaldosteronemic hyperpotassemia and low-renin hypertension showed seven members from three generations, who ranged in age from 4 to 56 years, to be affected. Results of earlier studies had established a normally functioning renin-aldosterone system and normal renal handling of potassium. 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 mmole/liter and proved proximal renal tubular acidosis (PRTA). Further, a linear increase in urinary fractional potassium excretion accompanied that of bicarbonate in both, as in normal individuals. Dextrose-insulin infusion in the brother failed to reduce hyperpotassemia. These data support the hypothesis that a generalized cell membrane defect that specifically impedes potassium influx (as opposed to an isolated renal tubular defect) underlies this autosomal dominant disorder.