This 12-week, open-label, multicenter study assessed the efficacy and safety of losartan/hydrochlorothiazide (HCTZ), alone or in combination with other antihypertensive agents, in the treatment of patients with severe systemic hypertension. Treatment began with once-daily losartan/HCTZ 50/12.5 mg. The dose was increased to 100/25 mg, if required, to achieve blood pressure (BP) control (sitting diastolic BP <95 mm Hg); felodipine (extended release) and/or atenolol could be added if target sitting diastolic BP was not achieved with losartan/HCTZ alone. Mean sitting systolic BP of the 131 patients enrolled was 165.3 mm Hg at baseline and 139.8 mm Hg at final visit (reduction -25.4 mm Hg; p < or =0.01). Mean sitting diastolic BP was 111.9 mm Hg at baseline and 93.6 mm Hg at final visit (reduction -18.4 mm Hg; p < or =0.01). After 2 weeks of treatment, 63.8% of patients (83 of 130) were taking losartan/HCTZ 50/12.5 mg alone. By the final visit, one third of patients (35.1%; 46/131) were still only taking losartan/HCTZ. Most patients (48.1%; 63 of 131) were taking losartan/HCTZ 100/25 mg plus felodipine (extended release) at the final visit. Losartan/HCTZ was well tolerated. Drug-related adverse experiences occurred in 30 patients (22.9%). Only 2 patients (1.5%) had a serious adverse experience; 6 patients (4.6%) discontinued the drug because of an adverse experience. In conclusion, losartan/ HCTZ, alone or as part of a regimen with other standard antihypertensive agents, is effective and well tolerated in the treatment of patients with severe hypertension.