Using a placebo baseline, positive controlled, double-blind, randomized titration to effect our study protocol, we assessed the antihypertensive actions of enalapril, hydrochlorothiazide, and their combination in 37 patients with moderate essential hypertension. Patients were maintained on their regular diets and received a placebo for 4 weeks. Patients with moderate systemic hypertension were randomized to receive enalapril monotherapy at a dose of 10 mg twice daily (n = 16), hydrochlorothiazide monotherapy at a dose of 25 mg twice daily (n = 15), or combination therapy consisting of 10 mg enalapril and 25 mg hydrochlorothiazide twice daily (n = 6). Therapy could be titrated to twice the starting dose. All treatment regimens reduced blood pressure, but only one patient had blood pressure normalized (diastolic blood pressure less than or equal to 90 mmHg) with enalapril (7%), two patients with hydrochlorothiazide (15%), and 80% of patients with combination therapy. The patients who had not achieved normal blood pressure received combination treatment, and after 8 additional weeks, more than 70% showed normal blood pressure. After one year of combination therapy, 92% of the patients continue to have normal blood pressure. Both the monotherapy and combination regimens were very well tolerated in this study. In conclusion, enalapril, hydrochlorothiazide, and their combination are effective in reducing blood pressure in patients with moderate hypertension. However, monotherapy is successful in normalizing blood pressure only in a small percentage of patients. Combination therapy achieved normalization of blood pressure in almost all patients, suggesting that most patients on regular diets with moderate hypertension may require a diuretic-ACE inhibitor combination rather than monotherapy to achieve effective blood pressure control.