We randomised ambulatory men with diastolic blood pressure (BP) 95-109 mmHg without anti-hypertensive medication to single drug treatment with either hydrochlorothiazide 12.5-50 mg/day, atenolol 25-100 mg/day, captopril 25-100 mg/day, clonidine 0.2-0.6 mg/day, diltiazem-SR 120-360 mg/day, prazosin 4-20 mg/day or placebo in a double-blind prospective trial. The assigned drug was titrated to a goal BP of < 90 mm Hg. Patients not achieving goal BP were rerandomised to an alternative single active drug. Non-responders to the second drug received the first drug in combination with the second. Of the 102 non-responders to both drugs who qualified for the combination, 59 (57.8%) responded. The combination pairs that included a diuretic achieved diastolic goal BP in 69% and < 140 mm Hg systolic in 77% compared with 51% and 46%, respectively, for those combinations without a diuretic (P = 0.067; P = 0.002). Six of the eight terminations due to adverse drug reactions were in combinations containing prazosin; three of these six were hypotensive reactions. We conclude that two single drugs of insufficient efficacy to control BP individually have a high probability of achieving goal BP when combined, especially if the combination contains a diuretic.