Effects of leukotriene (LT) C4 and LTD4 on coronary artery spasm in atherosclerotic miniature pigs were examined angiographically. Endothelial balloon denudation of the left circumflex coronary artery was performed in 15 Gottingen miniature pigs; 11 were fed a 2% cholesterol diet and four were fed a regular diet for 3 months. Three months after this denudation, the area of the coronary artery was reduced by 94 ± 2% and 43 + 5% (p < .01) in the denuded and nondenuded areas by the intracoronary administration of 10, g/kg histamine after pretreatment with 60 mg/kg iv cimetidine. The effects of LTC4 and LTD4 on coronary diameter and the preventive effects of FPL-557 12, a LTC4 and LTD4-receptor blocker, or diphenhydramine, a histamine HI-receptor blocker, on histamineinduced coronary spasm were then examined angiographically. Administration of LTC4 or LTD4 in doses of 1 and 10, ug into the left coronary artery, or selectively into the left circumflex and left anterior descending coronary arteries in a dose of 5, ug, led to the elevations in the ST segment on the electrocardiogram and there was delayed filling of the contrast medium in the peripheral coronary artery. However, these LTs provoked no augmented constrictions at any site on the epicardial coronary arteries (n = 15). Diphenhydramine, 1 mg/kg (n = 6), abolished the histamine-induced coronary spasm. FPL-55712, 0.1 mg/kg, with which the LT-induced myocardial ischemia was abolished, did not prevent the histamine-induced coronary artery spasm. Hence, in a swine preparation of coronary artery spasm, LTC4 and LTD4 constricted the coronary arteries at the level of small vessels and rendered the perfused myocardium ischemic. These compounds do not seem to play a primary role in the provocation of epicardial coronary artery spasm induced by histamine in this atherosclerotic swine preparation.