We studied the effect of intracoronary leukotriene B 4, C 4, D 4 and E 4 (0.1–3 μg) on coronary artery blood flow and resistance in anesthetized pigs. Conventional hemodynamics were measured, and the peripheral electrocardiogram was obtained in lead II. Thromboxane B 2 and 6-keto-prostaglandin F 1α (as breakdown products of thromboxane and prostacyclin, respectively) were measured during the influence of leukotrienes on the heart. All leukotrienes except B 4 reduced coronary flow. Peak reduction was produced by 3 μg of each eicosanoid: C 4= 96±4%+; D 4= 98±2%+; E 4= 82±8%+. Coronary resistance increased after the same dose B 4= 65±18%; C 4= 225±94%(P< 0.01); D 4= 442±118%+; E 4= 110±43%(+= P< 0.001). Increase in filling pressure and heart rate but blood pressure reduction and diminution in left ventricular d P d t max were observed with leukotriene C 4, D 4 and E 4. The ST segments of the electrocardiogram were elevated, thus indicating myocardial ischemia during the blood flow reduction. Indomethacin (5 mg/kg iv) had no effects on the leukotriene-induced hemodynamic sequelae. Thromboxane B 2 concentration in coronary sinus blood plasma increased by 132–176%(P< 0.05) at peak leukotriene effects on blood flow. Thus, leukotriene C 4, D 4, and E 4 are vasoconstrictors in the situ porcine heart. Leukotriene B 4, however, exerts no hemodynamic effects. The electrocardiographic ischemia and changes in hemodynamics indicate actions on coronary resistance and myocardial depression. These eicosanoids may contribute to cardiac dysfunction and vasospasm in coronary artery disease.