Hyperkalemia usually does not develop in chronic renal insufficiency until the glomerular filtration rate is very low. We studied 25 hyperkalemic patients with glomerular filtration rate ranging between 105 and 10 ml/min. 16 patients were unable to raise plasma aldosterone in response to hyperkalemia whereas the remainder of the patients increased plasma aldosterone to normal levels. Plasma cortisol levels were normal in both groups: At any given level of glomerular filtration rate, fractional potassium excretion, during baseline conditions, was significantly lower in both groups of patients than in controls. During stimulation of potassium excretion by NaHCO3, acetazolamide or Na2SO4 administration fractional potassium excretion was also lower in patients than in controls. Hyperchloremic metabolic acidosis was recognized in all but 2 patients of each group. These data indicate that hyperkalemia in patients with renal insufficiency, can arise either as a consequence of aldosterone deficiency or tubular unresponsiveness to this hormone.