To investigate the mechanism of action of nitrovasodilators in exercise-induced angina, 15 patients with chronic stable angina underwent a symptom-limited supine exercise test (exercise 1). After recovery, in 10 patients (group I) a coronary vasodilator, SIN-1 (the active metabolite of molsidomine) was injected into the most diseased coronary artery (80 µg in 4 min). In the remaining 5, a placebo was injected (group II). Immediately thereafter, the same exercise (exercise 2, identical workloads and exercise duration) was repeated. In group I, after intracoronary injection of SIN-1, the control values at rest (including pulmonary wedge pressure) did not significantly change. Heart rate, blood pressure and cardiac index rose in a similar way during exercises 1 and 2 (61, 20, 26 and 62, 21, 35%, respectively). However, 3 patients were angina-free without ST-changes during exercise 2. In the remaining 7, the ST/heart rate slope was reduced (60%; p < 0.02), the increase in pulmonary wedge pressure was less pronounced (p < 0.01) and ST-depression at end-exercise 2 was smaller: 1.3 ± 0.3 versus 2.1 ± 0.3 mm (p < 0.01) for identical work loads and double products. In group II, exercise 2 was identical to exercise 1 and the ST/heart rate slopes were quite reproducible. Therefore, these results argue for an improvement in coronary blood supply after intracoronary SIN-1 and suggest that the beneficial action of nitro vasodilators could be related to direct effects on the coronary circulation. However, the magnitude of this mechanism seems variable from one patient to another.