The efficacy of sustained-release diltiazem (diltiazem-SR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 12 patients with stable angina. Following a 1-week placebo period, patients received diltiazem-SR or metoprolol in two 3-week treatment periods, in a randomized double-blind crossover design. Total exercise time was increased more with diltiazem-SR than with metoprolol (1.2 min vs 0.4 min, P = 0.02), although the reduction in frequency of weekly anginal attacks was equal with both drugs (5 +/- 3 with placebo to 1 +/- 1 with both drugs). The difference between diltiazem-SR and metoprolol may, in part, be due to the fact that the tests were performed 12 h after drug administration. The diltiazem plasma levels were in the therapeutic range; metoprolol plasma levels, in contrast, were all below the therapeutic range. In addition, the patients might be tired out earlier during beta-blockade therapy, because a greater increase in exercise time with diltiazem-SR compared with metoprolol was found in those patients in whom the exercise endpoint changed from angina to fatigue. Thus, diltiazem-SR effectively reduces the frequency of anginal attacks when given twice daily, and improves exercise capacity to a greater extent than metoprolol 12 h after last dose.