The antianginal efficacies of nifedipine (40 to 120 mg/day) and diltiazem (120 to 360 mg/day) were studied in 21 normotensive patients with chronic stable angina pectoris, using a randomized, double-blind, crossover design. Patients received each agent titrated to maximum tolerated doses for 6 weeks, after a 2-week placebo baseline period. The maximum tolerated dose for nifedipine was 72 +/- 8 (standard error) mg/day and for diltiazem 297 +/- 20 mg/day. Two patients discontinued nifedipine early because of side effects. Duration of symptom-limited treadmill exercise was longer during the nifedipine (556 +/- 43 seconds) and diltiazem periods (546 +/- 39 seconds) compared with placebo baseline (474 +/- 41 seconds, p less than 0.02). Compared with placebo, nifedipine caused a significant increase in heart rate both at rest standing and at peak exercise. Nifedipine decreased resting systolic blood pressure but had no effect at peak exercise. In contrast, diltiazem caused a significant decrease in heart rate at rest but had no effect on blood pressure at rest or at peak exercise. Thus, nifedipine and diltiazem have differential effects on heart rate and systolic blood pressure suggesting different modes of action. However, despite the increase in exercise duration, neither nifedipine nor diltiazem increased the heart rate-systolic pressure product during maximum exercise. This suggests that the antianginal effects of the 2 agents probably are mediated via reduction of myocardial oxygen demand at submaximal exercise. In addition, diltiazem appears to be better tolerated than nifedipine.