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Spasm of large coronary arteries has been shown play an important role in the pathogenesis of a broad spectrum of ischemic heart disease, including variant angina, unstable angina, effort angina, and acute myocardial infarction [1-3]. Coronary artery spasm occurs in vessels with both angiographically absent or mild atherosclerotic narrowing and moderate or severe organic obstructions. However, the causes of coronary artery spasm are not yet clear. Numerous hypotheses including disturbances in central or local autonomic nervous control, abnormalities in platelet function, local metabolic derangements, altered reactivity of coronary artery, or a combination of these factors have been proposed as the causes of coronary artery spasm, but no conclusive evidence has been found. Some pharmacologic agents have been reported to provoke coronary artery spasm in patients with variant angina, and ergonovine maleate has been used clinically as the most specific and sensitive agent for diagnostic purposes [4-6]. There is accumulative evidence that atherosclerotic vessels from animals exhibited enhanced susceptibility to constrictor effects of ergonovine [7-9], histamine [10], and serotonin [7,8,11] and that they showed depressed responsiveness to some vasodilators [12]. We demonstrated that vascular smooth muscles in atherosclerotic arteries from cholesterolled rabbits or Watanabe heritable hyperlipidemic rabbits were supersensitive to ergonovine, which was at least partially mediated by a serotonergic mechanism [7,8]. In this report, vascular reactivity to vasoactive agents of isolated coronary arteries obtained at autopsy from a patient with documented variant angina was compared with that of coronary arteries from control subjects who had no detectable cardiac disease. To our knowledge, this is the first report to show that a spastic segment of coronary artery documented angiographically by ergonovine provocation testing during life was supersensitive to ergonovine in vitro, and it is concluded from this study that a supersensitivity of coronary arterial smooth muscles of localized segments rather than a hyper-reactivity is one of the most important fundamental mechanisms of coronary artery spasm., Spasms of coronary arteries underlie some heart dysfunctions, such as variant, unstable, and effort anginas and heart attacks, but the causes of such spasms are unclear. Certain vasoconstrictors, such as ergonovine, are used to test susceptibility to spasm in patients with variant angina, or angina at rest caused by coronary artery spasm. It is possible that atherosclerotic coronary arteries may be supersensitive and react more quickly to low doses of ergonovine, or they may be hyperreactive, reacting more strongly to regular ergonovine doses. A case is described of a man who developed coronary artery spasm following ergonovine treatment. After his death, a segment of the same artery was supersensitive to ergonovine. At age 58 the patient was diagnosed with moderate hypertension, and nine years later he suffered a heart attack. He had been in reasonably good health for six years when he developed variant angina, which became worse in spite of medication. Tests revealed obstruction and slight spasm of a coronary artery. The patient then was found to have lung cancer, of which he died at age 74. Following his death, laboratory tests for coronary artery disease and function were conducted as part of the autopsy. Ergonovine, but not the more physiological nerve-secreted hormones serotonin and phenylephrine, caused coronary artery constriction. The thickened, spastic segment of the coronary artery was responsive to one-thousandth of the ergonovine dose to which other artery segments were responsive. This finding suggests that supersensitivity of coronary artery cells to ergonovine and other vasoconstrictors is important in coronary artery spasm. (Consumer Summary produced by Reliance Medical Information, Inc.)