Background: The ��2 or ��2 adrenergic receptor in vasculature mediate vasoconstriction or dilation respectively in response to adrenergic agents, and ��1 adrenergic receptor in heart mediates chronotrophic and inotrophic changes. We investigate the relationship of vasospastic angina and four kinds of adrenergic receptor polymorphisms (��2 Del 322-325, ��2 Gly16, ��2 Glu27 and ��1 Arg389). Methods: Vasospastic angina (N=162) was confirmed by focal coronary spasm in CAG with chest pain or ST elevation on ECG after ergonovine intravenous infusion. Normal control group comprised 129 subjects who showed normal coronary angiogram. After a diagnostic coronary angiography was performed, four kinds of genotypes were identified separately using different PCR and RFLP methods from the DNA extracted from the peripheral monocytes. Results: The allele frequencies of four kinds of adrenergic receptor polymorphisms (��2 Del 322-325, ��2 Gly16, ��2 Glu27 and ��1 Arg389) in normal control were 0.23, 0.69, 0.53 and 0.17 respectively, and these are different from those of Caucasians (0.04, 0.61, 0.43, 0.73). The differences were prominent in ��2 Del 322-325 and ��1 Arg389. The frequencies of ��2 Del 322-325 polymorphism were significantly higher in variant angina group than in control, 16.4% and 0.8% respectively (p<0.0001). The ��2 polymorphism of codon 27(Glu27) is much less frequent in variant angina group than in control(29.3% : 49.3%, p<0.0001). However, there was no difference in the prevalence of ��2 polymorphism of codon 16(Gly16) or ��1 polymorphism between the two groups. Conclusion: The Del (322-325) mutant of ��2 receptor is a new genetic risk factors for variant angina, and Glu27 allele of the ��2 adrenergic receptor is a negative risk factor for variant angina. This is the first report in the world to demonstrate the contribution of genetic characteristics of the vascular adrenergic system to coronary vasospasm.