The effects of leukotriene (LT) D4 (0.5 microgram/min) infusion into the left anterior descending coronary artery (LAD) of anesthetized pigs were studied in the absence or presence of indomethacin (5 mg/kg i.v.). In some pigs, arteriocoronary venous (A-V) blood plasma concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured by RIA technique during LTD4 actions. LTD4 changed LAD blood flow at 5 and 30 s, 2, 4 and 5 min by -46% (p less than 0.01), -93% (p less than 0.001), -45% (p less than 0.01), -28% (p less than 0.05) and 16%, respectively. Thus, the coronary constriction disappeared despite sustained LTD4 infusion and was followed by reactive hyperemia. Indomethacin did not affect the coronary flow or hemodynamic responses to LTD4 infusion. The A-V difference in prostanoids did not change during LTD4 administration. Cyclooxygenase products of arachidonic acid may not be responsible for early constriction and later escape phases of LTD4 effects on the coronary circulation. However, intracoronary bolus injection of LTD4 stimulated prostacyclin release from the vasculature in a dose-dependent manner causing significant reactive hyperemia after temporary blood flow cessation. Release of a LTD4-induced vasodilating factor from the coronary vessels unrelated to prostanoids may cause escape from vasoconstriction during LTD4 infusion.