This randomized, double-masked, multicenter, clin. study with 3 parallel treatment groups was conducted to compare the efficacy and tolerability of losartan, alone or combined with hydrochlorothiazide (HCTZ), and amlodipine in patients with mild-to-moderate hypertension. A 4-wk placebo period was followed by a 12-wk treatment period. A total of 935 patients were randomized to 3 treatment regimens: losartan at 50 mg once daily with a possible increase to 100 mg once daily (L50/100), losartan at 50 mg once daily with a possible addition of HCTZ at 12.5 mg once daily (L/HCTZ), or amlodipine at 5 mg once daily with a possible increase to 10 mg once daily (A 5/10) at week 6. Approx. 50% of the patients in each treatment group required a dose adjustment because of inadequate response. At the end of the study the reductions in mean trough sitting diastolic blood pressure (SiDBP) were -11.4, -13.2,, and -13.6 mm Hg in the L 50/100, L/HCTZ, and A 5/10 treatment groups, resp. Reductions in mean trough sitting systolic blood pressure (SiSBP) were similar in all treatment groups. Blood pressure reductions (SiSBP/SiDBP) were comparable in the 2 subgroups without dose adjustment (-18.6 mm Hg/-14.2 mm Hg for losartan 50 mg and -19.0 mm Hg/-14.8 mm Hg for amlodipine 5 mg) during the 12-wk treatment period. Differences between the treatment groups in patient-reported symptoms were significant, with a higher rate of swelling and edema reported with amlodipine (10%) than with losartan (3%). Overall, losartan appeared to be as effective as amlodipine and to have fewer drug-related side effects.