Recent studies in isolated epicardial coronary artery rings have shown that the endothelium modulates vasomotor responses to certain endogenous neurohumoral agents. It is not known whether the endothelium plays a role in large coronary vasoregulation in the intact coronary circulation. Accordingly, we examined effects of endothelial removal on vasoconstrictor responses of the proximal coronary artery in anesthetized adult mongrel dogs. The left anterior descending artery was perfused at 100 mm Hg with arterial blood from a pressurized reservoir. Coronary diameter was measured continuously with 7-MHz sonomicrometer crystals attached to the adventitia of the artery. Fifteen minutes after mechanical disruption of the endothelium with a balloon-tipped catheter, baseline diameter was unchanged from a control value of 2.60 +/- 0.13 mm (mean +/- SE, n = 17). Endothelial denudation resulted in a dose-dependent potentiation of the constrictor response to intracoronary 5-hydroxytryptamine (1-50 micrograms/min, n = 8). With the endothelium intact, a 5 micrograms/min infusion of 5-hydroxytryptamine reduced diameter by 24 +/- 14 micron, while a 50 micrograms/min dose reduced diameter by 54 +/- 25 micron. After endothelial removal, the decrease in diameter averaged 74 +/- 18 microns at 5 micrograms/min and 132 +/- 29 micron at 50 micrograms/min, indicating a 10-fold increase in the sensitivity to 5-hydroxytryptamine. The constrictor responses to angiotensin II (1 and 5 micrograms/min, n = 7) and phenylephrine (1-5 micrograms/min, n = 7) were not altered by endothelial removal. Thus, endothelial removal selectively potentiates the constrictor responses to 5-hydroxytryptamine in the intact coronary circulation of the dog.