Sixty-three patients with stable angina New York Heart Association (NYHA) class III and a positive stress test despite triple therapy were randomized to a double-blind protocol, receiving either placebo or amiodarone in a dose of 600 mg/day for 10 days, followed by 400 mg/day for an additional 10 days, and then by 200 mg/day over a total period of 2 months. Comparable bicycle exercise times were observed at baseline in the amiodarone group (6.0 +/- 1.6 minutes) and in the placebo group (6.0 +/- 1.8 minutes). With amiodarone, there was a increase in exercise duration of 6.7 +/- 2.2 minutes versus 6.3 +/- 2.2 minutes at 1 month and 7.5 +/- 2.1 minutes versus 6.2 +/- 1.7 minutes at 2 months (p < 0.05). Also, the amiodarone group had a significant decrease in the double product when compared with the placebo group at 1 month (14,134 +/- 3,316 versus 17,570 +/- 4,092 mm Hg/min, p < 0.001) and at 2 months (14,022 +/- 3,303 and 17,298 +/- 4,872 mm Hg/min, p < 0.001). The degree of ST segment depression at peak exercise was also significantly reduced. Combination therapy of amiodarone with conventional antianginal therapy is well tolerated and results in a significant improvement in exercise capacity and a mild reduction of symptoms in patients who have continued, limiting angina pectoris with conventional triple therapy.