In order to assess the long-term efficacy of diltiazem for the treatment of angina pectoris, eight patients with chronic stable exertional angina who were previously entered into a 4-month randomized, double-blind placebo controlled study, were studied for an additional 12-months. The patients continued to take diltiazem, 360 mg/day, and underwent treadmill exercise testing after 10 and 16 months of therapy. A single-blind placebo week was introduced after 16 months and a treadmill test was performed at the end of this week. Diltiazem therapy continued to augment exercise duration until 0.1 mV of ECG ST depression at 10 and 16 months as compared to the final placebo period: 573 +/- 133 (SD) seconds at 10 months; 565 +/- 148 seconds at 16 months; vs 431 +/- 151 seconds at final placebo (both p less than 0.001). Also, the time to angina pectoris was prolonged on diltiazem by 181 seconds at 16 months (p less than 0.01) and the total duration of exercise was increased by 101 seconds (p less than 0.001) as compared to placebo. In addition, angina frequency decreased from 17 +/- 11 attacks/week on placebo to 0.6 +/- 0.6 attacks/week during diltiazem therapy at 16 months. Two of the eight patients noted mild pedal edema, but no other adverse effects were experienced. Thus diltiazem, 360 mg/day, can be an effective single agent for the long-term treatment of chronic stable angina pectoris.