Seventeen patients (11 males) 34-66 years in age with uncomplicated essential hypertension completed a randomized, placebo-controlled, double-blind cross-over study comparing indapamide (IND) 2.5 mg q am with hydrochlorothiazide (HCT) 50 mg q am. The lead-in placebo period of 2 months was followed by two active drug phases of 3 months' duration separated by a 2-month placebo-washout period. The mean standing systolic/diastolic pressures (+/- SD) during placebo were 150 +/- 18/98 +/- 6 mm Hg. The pressures were 137 +/- 16/90 +/- 7 IND and 137 +/- 17/91 +/- 7 mm Hg on HCT. Thus the drugs produced similar systolic, diastolic, and mean arterial pressures. Orthostatic changes in mean pressure and heart rate were similar with the two drugs. Both drugs decreased serum potassium (-14.3% with IND and -13.7% with HCT), and increased serum uric acid (+26.7% with IND and +25.7% with HCT), and cholesterol (+11.7% with IND and +11.1% with HCT) equally. Forearm blood flow (FBF) and venous compliance (FVC) were measured by a plethysmographic technique in six of the patients. FBF during placebo of 3.53 +/- 0.58 ml/min/100 ml forearm volume was increased to 4.01 +/- 0.74 ml/min during IND and decreased to 3.40 +/- 1.16 ml/min on HCT, but our sample size did not permit detection of significant differences. FVC was not altered from baseline by the drugs. No side effects attributable to either of the two drugs were elicited. We conclude that IND did not differ from HCT in its effect on blood pressure, heart rate, venous compliance, or biochemistry. A possible peripheral arteriolar vasodilator effect on IND should be investigated further.