In a multicenter, multinational study, 200 patients with essential hypertension were treated with a fixed dose of Enalapril (E) 20 mg/day after a 2- to 4-week placebo period. All had diastolic blood pressure (DBP) 100 to 120 mm Hg at the end of the placebo period. They were then given E for 6 weeks. If DBP after this was greater than 90 mm Hg they were randomized double-blind to added therapy with hydrochlorothiazide (H) either 25 mg/day (E + H 25) or 12.5 mg/day (E + H 12.5) or placebo (E + P) for 4 weeks. Blood pressure was measured approximately 24 hours after taking the medication. In the whole group, BP fell from 171/107 to 156/97 mm Hg during monotherapy with E (P less than 0.001). Sixty-six patients reached DBP less than or equal to 90 mm Hg on E alone. Of the remainder, 42 were randomized to E + P. In these, BP fell by 5.9/3.4 mm Hg (P less than 0.05). Forty-two patients received E + H 12.5 and BP fell by 9.0/6.9 mm Hg (P less than 0.001). Forty-one patients received E + H 25 and BP fell by 5.6/6.3 mm Hg (P less than 0.05/0.01). The proportion of patients who reached DBP less than or equal to 90 mm Hg was 26% in the E + P group, 48% in the E + H 12.5 group (P less than 0.05 compared to E + P group), and 38% in the E + H 25 group. There were no other significant differences between the E + H 12.5 and E + H 25 groups except that S-potassium fell significantly (-0.2 mmol/L) in E + H 25. Both regimens were remarkably well tolerated. It can be concluded that H 12.5 mg/day potentiates the effect of Enalapril 25 mg/day at least as well as H 25 mg/day and better than placebo.