The antihypertensive effects and the tolerability of losartan and enalapril given alone or in combination with hydrochlorothiazide (HCTZ) were compared in a multicenter, double-blind, randomized, parallel-group, 16-week clinical trial. The study consisted of a 4-week placebo washout phase and a 12-week active treatment phase. Patients with mild-to-moderate, uncomplicated essential hypertension were considered for participation in the study. To enter the treatment phase of the study, a mean sitting diastolic blood pressure (SiDBP) > or = 95 and < or = 115 mm Hg was required. Patients received either 50-mg losartan once daily or 5-mg enalapril once daily at randomization. The dose of enalapril could be titrated to 10 mg after 4 weeks and 25 mg of HCTZ could be added after 8 weeks, based on measurements of SiDBP at clinic visits. The dose of losartan remained at 50 mg; 12.5 mg of HCTZ could be added after 8 weeks. Changes in the treatment regimen at each step were required if SiDBP remained > or = mm Hg. Doses of the diuretic were chosen based on commercially available forms of the test agents in combination with HCTZ. Trough blood pressure, heart rate, and safety parameters were measured at 4-week intervals during the treatment phase of the study. Significant reductions in mean SiDBP and mean sitting systolic blood pressure (SiSBP) were achieved at all time points (4, 8, and 12 weeks) with both treatments. No significant differences between treatment groups for mean changes in SiDBP or SiSBP were observed overall. At study end, patients receiving the losartan regimen had a mean reduction in SiDBP of 10.3 mm Hg, whereas patients in the enalapril regimen had a mean reduction of 9.8 mm Hg. Likewise, the percentage of patients reaching goal blood pressure reduction was not significantly different between groups. The mean reduction in SiDBP-- but not SiSBP--in black patients was slightly greater in the losartan group than in the enalapril group (SiDBP, 10.0 mm Hg losartan vs 8.0 mm Hg enalapril; P = 0.02). Similarly, losartan patients aged 65 years and older had a slightly greater decrease in SiDBP than comparable enalapril patients (12.7 mm Hg vs 8.7 mm Hg; P = 0.03). The importance of these differences between subgroups must be clarified by additional studies. Overall, both treatments were well tolerated. A regimen of losartan alone or in combination with HCTZ was effective in treating patients with essential hypertension and was comparable to a regimen of enalapril alone or in combination with HCTZ. However, treatment with losartan was associated with a lower incidence of cough.