A multicenter, randomized, placebo-controlled, double-masked, parallel-group study was performed to compare the efficacy and safety of valsartan 20, 80, 160, and 320 mg with placebo in the treatment of patients with essential hypertension. A total of 736 adults with uncomplicated essential hypertension stages 1 to 3 were randomized to receive placebo or valsartan 20, 80, 160, or 320 mg daily for 8 weeks. Assessments were made at baseline, after 4 and 8 weeks of treatment, and 2 to 3 days after stopping treatment. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure (MSDBP). Other variables included change from baseline in mean sitting systolic blood pressure (MSSBP) and responder rates (ie, MSDBP < 90 mm Hg or decrease of > or = 10 mm Hg from baseline). All doses of valsartan produced statistically significant reductions in both MSDBP and MSSBP at end point compared with placebo. A dose-response effect was seen, although the incremental reduction in blood pressure with doses of valsartan > 80 mg was relatively small. Statistically significant differences in responder rates at end point were seen for doses of valsartan of 80 mg and above compared with placebo, whereas the responder rates for valsartan 20 mg was not significantly different from that for placebo. Safety and tolerability variables included data on adverse experiences, rebound hypertension, and clinical laboratory evaluations. Tolerability was good, with headache being the most common complaint and occurring most frequently in placebo patients. The incidence of dizziness was similar among the placebo (5.4%) and valsartan 20-mg to 160-mg groups (2.1% to 3.4%); there was an increase in the incidence of dizziness in the 320-mg group (9.3%). No cases of symptomatic orthostatic hypotension occurred. Analysis of rebound showed that 11.6% of patients receiving placebo and 16.6% receiving valsartan had an increase in MSDBP to baseline levels or above 2 to 3 days after stopping treatment. No clinically significant adverse experiences were noted after stopping treatment. There were no clinically or statistically significant changes in laboratory values during treatment. Thus valsartan proved to be both effective and safe in reducing blood pressure in adults with essential hypertension. The optimal dose range is 80 to 160 mg, given once daily.