The aldosterone response to increments in plasma potassium concentration in disease states associated with abnormal potassium tolerance remains undefined. We evaluated the plasma aldosterone response to an acute oral potassium load (0.25-0.50 mmol/kg body weight) in 30 patients (19 with chronic renal failure (CRF) and 11 with diabetes mellitus) with normal or decreased baseline plasma aldosterone levels and in 12 control subjects. In control subjects, plasma aldosterone levels increased initially and then declined below baseline, whereas in the patients the late decrease was not observed. In patients with CRF with and without hypoaldosteronism (5 undialyzed and all 9 dialyzed patients), plasma aldosterone increased significantly. Eight of the diabetic subjects had normal and 3 had low baseline aldosterone levels. In the former, plasma aldosterone levels did not increase above baseline following the KCl load. We conclude that diabetic patients and those with CRF manifest several abnormalities in aldosterone-potassium responsiveness that may contribute to the disturbed potassium homeostasis observed in these conditions.