We studied the effect of acetazolamide on plasma potassium in normals and in two patients with hyperkalemic periodic paralysis. Administration of acetazolamide for 48 hours lowered mean plasma potassium in normals from 4.01 to 3.56 mEq per liter (p less than 0.001) and in the patients from 4.55 to 4.00 mEq per liter (p less than 0.001). This kaliopenic effect of acetazolamide may account for its therapeutic action in hyperkalemic periodic paralysis.