Diuretic therapy is still regarded as the first-step approach in elderly patients with benign or moderate arterial hypertension. Traditional preparations such as thiazides, or potassium-sparing agents, are not devoid of significant side effects, however. Indapamide, a nonthiazide diuretic, has been shown to reduce blood pressure at low doses, in several clinical reports. In the present study, the effect of indapamide (2.5 mg per day) was compared with that of hydrochlorothiazide (50 mg per day) on blood pressure and serum chemistry of 47 elderly hypertensive patients (ages 65 to 91). After a six-week placebo-treatment period, patients were randomly assigned to receive either indapamide or hydrochlorothiazide. At that moment, blood pressure of patients in the supine position averaged 185± 2/107 ± 2, and 181 ± 3/102 ± 2 mm Hg, in the indapamide and hydrochlorothiazide groups, respectively. After 48 weeks of therapy, blood pressure was 162 ± 3/89 ± 2 and 170 ± 2/94 ± 2 mm Hg in the same groups, respectively. Serum sodium levels remained unchanged in indapamide-treated patients, but decreased progressively from 141 ± 1 to 134 ±1 meq/liter in hydrochlorothiazide-treated patients. Serum potassium levels decreased from 4.50 ± 0.12 to 4.04 ± 0.10 meq/liter in indapamide-treated patients, whereas in the patients receiving hydrochlorothiazide, kalemia decreased from 4.23 ± 0.09 to 3.33 ± 0.01 meq/liter. Finally, serum uric acid levels did not increase significantly in patients receiving indapamide, whereas it rose from 6.5 ± 0.4 to 8.7 ± 0.3 mg/dl in patients treated with hydrochlorothiazide. In conclusion, indapamide resulted in a better control of systolic and diastolic blood pressure in this group of elderly hypertensive patients, in addition, the effect of each drug on blood chemistry differed markedly: indapamide failed to alter significantly the serum ionic composition, whereas hydrochlorothiazide was associated with both hyponatremia and hypokalemia.