ObjectiveTo establish the optimal dose of the perindopril/indapamide combination (Per/Ind) in the treatment of mild or moderate hypertension.DesignThis was a randomized, double-blind, placebo-controlled, seven-way parallel-group, dose-ranging study, set in multicenter, outpatient offices/clinics in Europe and Canada.PatientsA total of 438 patients aged between 18 and 75 years whose supine diastolic blood pressure was between 95 and114 mmHg were randomly assigned to an 8-week double-blind treatment with either placebo, Per 2/Ind 0.625, Per 4/Ind 1.25, Per 8/Ind 2.5, Per 0/Ind 1.25, Per 2/Ind 1.25 or Per 8/Ind 1.25 mg.Main outcome measuresSystolic and diastolic blood pressure measured in the clinic approximately 24 h after dosing.ResultsThere was a linear dose–response relationship (P= 0.001) for doubling the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressive fall in supine diastolic blood pressure (−9.3 to −15.0 mmHg). Combining 1.25 mg Ind with increasing doses of Per (0, 2, 4 and 8 mg) also showed a linear dose–response relationship (P<0.001), with supine diastolic blood pressure falling by −8.0 to −12.0 mmHg compared with a fall of −5.2 mmHg for the placebo group. Similar findings were noted for supine systolic blood pressure, standing blood pressure and ambulatory blood pressure. Hypokalemia was more common (9.7%) in the Per 8/Ind 2.5 mg group than in the groups receiving other doses (0–4.6%).ConclusionThe combinations of Per 2/Ind 0.625 mg and Per 4/Ind 1.25 mg were effective in reducing blood pressure without producing clinically important side effects.