In open chest dogs, studies were made of the effects of intravenous trinitroglycerin (10 micrograms/kg per min) on circumflex arterial coronary blood flow, coronary vascular resistance, systemic arterial pressure and myocardial prostaglandin E production before and after indomethacin (n = 9) or indomethacin vehicle (n = 5). During a 30 minute trinitroglycerin infusion, coronary sinus prostaglandin E concentration increased significantly (approximately +41 percent, p less than 0.01) without significant changes in left atrial prostaglandin E concentration. After indomethacin (5 mg/kg), but not indomethacin vehicle alone, a second trinitroglycerin infusion (10 micrograms/kg per min) produced a significantly smaller decrease in coronary vascular resistance (p less than 0.05) and systemic blood pressure (p less than 0.01) and no increase in coronary sinus prostaglandin E (p less than 0.001) by comparison with control values. The heart rate response to trinitroglycerin was significantly greater (p less than 0.05) after than before indomethacin. This study suggests that the mechanism of action of trinitroglycerin may be at least partially mediated through the prostaglandin system.