In a double-blind randomized study, we evaluated the effects of 25 mg vs 50 mg of hydrochlorothiazide in 51 elderly patients (aged 68.9 +/- 7.0 years) with isolated systolic hypertension (blood pressure, 160 to 239 mm Hg systolic and less than 90 mm Hg diastolic). Dose levels could be increased to twice daily to control blood pressure. The reductions in blood pressure (25.4/6.8 mm Hg and 28.9/7.4 mm Hg) and proportion of patients in whom blood pressure was controlled (78% and 89%) were similar in the lower- and higher-dose groups during the titration phase. However, serum potassium level was reduced more in the higher-dosage (0.57 mmol/L) than the lower-dosage (0.17 mmol/L) group. There were no significant changes in blood pressure during a 24-week maintenance phase. No patient required withdrawal from the study because of adverse effects, and cognitive-behavioral function was well preserved. We conclude that hydrochlorothiazide is effective and well tolerated in older patients with isolated systolic hypertension, many of whom may be effectively treated with 25 mg of hydrochlorothiazide once daily.