A randomized, double-blind, multicenter study comparing amiloride hydrochloride, amiloride hydrochloride plus hydrochlorothiazide, and hydrochlorothiazide was conducted in 179 patients with mild to moderate essential hypertension (diastolic pressure, 95 to 115 mm Hg). After 12 weeks of treatment, significant reductions in pressure were observed for all three treatment groups. Systolic pressure reduction was greatest for amiloride plus hydrochlorothiazide. Baseline vs 12-week average supine pressures were 153/101 vs 139/93 mm Hg for amiloride, 160/100 vs 137/90 mm Hg for amiloride plus hydrochlorothiazide, and 154/101 vs 134/89 mm Hg for hydrochlorothiazide. Baseline vs treatment mean serum potassium levels were 4.24 vs 4.47 mEq/L for amiloride, 4.24 vs 3.86 mEq/L for the combination, and 4.15 vs 3.56 mEq/L for hydrochlorothiazide. The changes in serum potassium level from the baseline for amiloride plus hydrochlorothiazide were significantly different from those for hydrochlorothiazide throughout the study (except for week 6). All drugs were well tolerated, and no drug-related toxic reaction was detected. This study demonstrates the efficacy of amiloride and amiloride plus hydrochlorothiazide as diuretic antihypertensive potassium-conserving agents.