In order to assess the role of alpha-adrenergic coronary tone in exercise-induced ischemia, 23 patients with chronic stable angina underwent, after coronary angiography, a symptom-limited supine exercise test on a cyclo-ergometer. After recovery, either phentolamine (for the first nine patients) or indoramin (for the following nine patients) was directly injected into the most diseased vessel at identical doses (2 mg over 5 min). In the remaining 5 patients, a placebo was injected. Immediately thereafter the same exercise (identical workloads and exercise duration) was repeated. During exercise 1, heart rate (HR), mean blood pressure, and cardiac index increased by 51%, 23% and 33% in the phentolamine group, and by 45%, 15%, and 33% in the indoramin group. After intracoronary injection of phentolamine or indoramin, control values (including pulmonary artery wedge pressure (PA wedge] at rest did not change significantly. During exercise 2, HR, mean blood pressure, and cardiac index increased in a similar way; however, the increase in PA wedge was less pronounced (p less than 0.01 in the phentolamine group and p less than 0.05 in the indoramin group). ST-segment depression at the end of exercise 2 was significantly smaller for identical workloads and double products in the phentolamine group: 1.5 +/- 0.3 mm vs 2.5 +/- 0.3 mm (p less than 0.01). However, these changes did not reach a statistical significance in the indoramin group: 1.7 +/- 0.2 mm vs 2.0 +/- 0.1 mm (NS). ST/HR slope in exercise 2 decreased by 51% (p less than 0.01) in the phentolamine group and by 34% (p less than 0.05) in the indoramin group. In the placebo group, exercise 2 was identical to exercise 1 and the ST/HR slopes were quite reproducible. These results show a less severe ischemic response after intracoronary alpha-blockade. Therefore, our results argue for a role of alpha-adrenergic coronary tone in exertional angina. The relatively higher efficiency of phentolamine vs indoramin suggests that alpha 2-adrenergic mechanisms contribute to the inappropriate coronary vasoconstriction during exercise in these patients.