Fantofarone is a calcium channel antagonist of a class (sulfone indolizine) that is structurally different from the existing classes. The primary cardiac action of fantofarone is on the sinus node, although it is also a potent peripheral and coronary vasodilator. This is a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluating the efficacy and safety of fantofarone. Three hundred and thirty patients were included as intent-to-treat, and 299 patients completed the entire protocol. Doses of fantofarone studied were 50, 100, 150, and 200 mg twice daily. The 100- and 150-mg groups demonstrated antianginal activity, prolonging exercise time walking on a treadmill by 38 and 45 seconds to the endpoint of moderate angina, compared with the placebo group. Sinus bradycardia occurred in 23 patients and was somewhat dose-related. Systolic blood pressure at rest and while exercising was not altered by therapy. No deaths occurred in the treated group. Of the 20 patients in the treatment group who did not complete the protocol (compared with 23 in the placebo group) 6 were dropped because of symptomatic bradycardia, 5 because of increased angina, and 9 for miscellaneous reasons. In doses of 100 mg to 150 mg twice daily, monotherapy fantofarone was effective and safe in the treatment of patients with chronic, stable angina pectoris.