This was a randomized double-blind, multiclinic, parallel, three treatments group study to compare the safety and efficacy of a fixed-ratio combination of enalapril/hydrochlorothiazide (E/HCTZ: 20/12.5-40/25 N = 46) to enalapril (E = 20-40 mg, N = 49) and hydrochlorothiazide (HCTZ: 12.5-25 mg, N = 51) once daily, in the treatment of patients with moderate to severe essential hypertension (100 less than or equal to supine diastolic blood pressure less than or equal to 120 mmHg). A significant decrease of systolic and diastolic blood pressure was shown in the 3 subgroups of patients. The decrease of blood pressure was significantly greater in the E/HCTZ subgroup. After 8 weeks of treatment, the E/HCTZ group had the greatest proportion of normotensive patients (65.9 p. cent, DBP less than or equal to 90 mmHg) and of responders (81.8 p. cent, diastolic blood pressure decrease greater than 10 mmHg). The treatment groups did not differ significantly with respect to clinical adverse events. The study results document the well-known hyperuricemic effect of diuretics and also indicate that the combination of enalapril and HCTZ ameliorates this effects. In this study plasma potassium was slightly but not significantly decreased by HCTZ. The combination of enalapril and hydrochlorothiazide did not alter this parameter. The results support the conclusion that in the treatment of moderate to severe hypertension, the combination enalapril/HCTZ 20/12.5 to 40/25 mg, taken once daily, is more effective than either its components used alone. This combination is well tolerated, probably due to an adequate enalapril/HCTZ dosage ratio.