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The Angiotensin I-converting enzyme (ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cardiovascular diseases. Previous studies showed that deletion polymorphism in the ACE gene might be a risk factor for myocardial infarction in the Caucasian population. However, this finding has not yet been reported in the Japanese population. In this study, a 287 base pair (bp) insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction (PCR) in a cross-sectional study of 35 healthy subjects and 85 patients with ischemic heart diseases (IHD) (32 angina pectoris, 53 myocardial infarction). Polymorphism of the ACE gene was characterized by three genotypes; two deletion alleles (genotype DD), two insertion allele (genotype II) and heterozygotes alleles (genotype ID). No differences could be detected among the three genotypes for total cholesterol, high-density lipoprotein cholesterol, blood pressure and body mass index. The serum ACE activities in each II, ID and DD genotype were 10.1 +/- 2.1 microU/ml, 13 +/- 3.2 microU/ml, 14.2 +/- 5.4 microU/ml, respectively. In the population study the genotype DD was significantly associated with IHD when compared with the other two genotypes (ID and II). The frequency of deletion allele was higher (0.61) in the IHD group than in the normals (0.39) (chi 2 = 7.8, p < 0.01). These frequencies were not varied whether they had classic risk factors or not. Furthermore, coronary multivessel impairment was significantly associated with the deletion allele than with the insertion allele (chi 2 = 11.7, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)