The acute effects of slow-release nifedipine and isosorbide dinitrate on exercise tolerance were compared in nine patients with isolated total coronary artery occlusion showing retrograde filling via collaterals. All patients had a reproducible positive exercise stress test off medication before the study. Each patient was randomized to 10 mg slow-release nifedipine and 5 mg isosorbide dinitrate in a single-blind, cross-over study. The exercise stress test was performed 30 minutes after drug administration. After nifedipine, three patients had a negative exercise stress test, whereas the test was negative after isosorbide dinitrate only in one patient. A significantly higher exercise tolerance was detected at peak exercise after nifedipine than after isosorbide dinitrate, as shown by a longer exercise time (380 +/- 44 vs. 295 +/- 41 seconds, p less than 0.001), a more increased maximum work load (355 +/- 89 vs. 255 +/- 55 W x min, p less than 0.02), and a higher rate-pressure product (30,300 +/- 2,500 vs. 26,100 +/- 2,700, p less than 0.01). In conclusion, these results seem to suggest that nifedipine may have a vasomotor effect on collaterals, since it elevated the threshold of ischemia more than isosorbide dinitrate did in patients with isolated coronary artery occlusion, showing retrograde filling via collaterals.