Mibefradil, a tetralol derivative, is the first representative of a new class of calcium antagonists. It selectively blocks entry of calcium into cells through T-type channels. The efficacy and tolerability of mibefradil in the treatment of mild-to-moderate essential hypertension were evaluated in four placebo-controlled, double-blind, dose-finding studies involving over 1000 patients. Two trials involved patients from the general population, one examined a subpopulation of elderly patients, and one evaluated patients receiving chronic hydrochlorothiazide (HCTZ) treatment. Based on these studies, the recommended doses of mibefradil are 50 mg and 100 mg. Doses >100 mg/day were associated with small gains in efficacy and an increased incidence of adverse effects. Response (sitting diastolic blood pressure normalization to < or =90 mm Hg or reduction by > or =10 mm Hg) rates to mibefradil ranged from 46.0% to 68.6% with 50 mg, and from 60.0% to 93.2% with 100 mg. Normalization rates paralleled the response rates, ranging from 34.0% to 62.9% with 50 mg, and from 42.5% to 81.8% with 100 mg. The effects on sitting systolic blood pressure were similar. Treatment was associated with a slight, potentially beneficial reduction in heart rate. Results were similar across all populations, indicating that no dose adjustment is required for elderly and for HCTZ-treated patients. The frequency of adverse events was similar to that reported for placebo groups, with headache being the most common complaint. In comparative trials, mibefradil was more effective than nifedipine SR and diltiazem CD, and at least as effective as amlodipine and nifedipine GITS. Overall, mibefradil was better tolerated than the comparison drugs. Mibefradil, at the recommended doses of 50 to 100 mg/day, is safe and effective for the treatment of mild-to-moderate hypertension.