To establish the frequency and clinical and biochemical characteristics of hyporeninemic hypoaldosteronism (HH), we reviewed 100 consecutive cases of hyperkalemia (potassium content > 5.3 mEq/L). The most common cause was end-stage renal failure (34%). Other causes included overzealous potassium replacement, spironolactone therapy, hemolysis, acute renal failure, acidosis, thrombocytosis, and Addison's disease. Ten of 19 patients with unexplained hyperkalemia showed suppressed renin (0.12 to 1.3 ng/mL/hr) and aldosterone (5.4 to 21.6 ng/dL) responses to furosemide-posture challenge. Cortisol reserve was normal in HH. Fludrocortisone acetate therapy corrected the hyperkalemia. Other features of HH include low serum bicarbonate content, mild renal insufficiency, diabetes, and advanced age. The use of indomethacin and ibuprofen was associated with one case of HH each. Results suggest that HH is an overlooked cause of hyperkalemia, especially in patients whose hyperkalemia is unexplained.