The effect of long-term administration of acetazolamide on the potassium balance of 15 glaucoma patients was studied. Average duration of treatment was two years. No total body potassium depletion was noted; serum potassium was below normal in one case (3.1 mEq/liter). Administration of potassium chloride (average dose, 58 mEq daily) did not cause a lowering of intraocular pressure; nor did it appear to alter potassium balance. Patients receiving long-term treatment with acetazolamide were unable to excrete concentrated urine (serum osmolarity per urine osmolarity ratio of 1:2.3 after an 18-hour fast). Three of 15 patients developed urinary tract disease. Patients on long-term acetazolamide therapy rarely need supplemental potassium. Where advisable, it is best provided by a diet high in potassium-rich foods, as enteric-coated preparations may cause small-bowel ulceration.