Several studies have shown that 5 mg amiloride can counteract the hypokalemic effect of 50 mg hydrochlorothiazide (HCTZ). In a double-blind study of 30 subjects with mild to moderate primary hypertension, we determined whether this effect could be obtained with half the dose of amiloride (2.5 mg) in combination with 25 mg HCTZ. The effect of twice the dosage was evaluated in subjects with unsatisfactory blood pressure (BP) on the lower dose. Both 25 mg HCTZ/amiloride 2.5 mg and 25 mg HCTZ alone lowered BP. In subjects with untreated diastolic BP between 110 and 115 mm Hg, these doses were inadequate; twice the dose resulted in a greater reduction in BP. Irrespective of dosage, a potassium-sparing effect resulted from the combination of HCTZ and amiloride, with a reduction in serum potassium levels from HCTZ alone as well.