Potassium supplementation in diuretic-induced hypokalemia (serum potassium less than 3.5 mmol/liter) in patients being treated for hypertension is a common event. In a previous study 40 mmol/day of orally administered potassium was not effective in preventing diuretic-induced hypokalemia in patients who had previously developed hypokalemia while being treated for hypertension with hydrochlorothiazide. In the study reported here dosages as high as 60 to 80 mmol/day of orally administered potassium failed to prevent hypokalemia in 7 of 19 hypertensive patients who were receiving hydrochlorothiazide. Potassium supplementation was compared with the potassium-sparing diuretic amiloride. The study design was open label and subject matched with crossover of therapeutic regimens.