The relationship between coronary artery disease (CAD) and polymorphisms of genes encoding angiotensinogen (AGT) and angiotensin converting enzyme (ACE) was analyzed in Japanese subjects. One hundred and four patients with CAD and 170 healthy subjects were enrolled in the study. CAD was defined as having a luminal diameter stenosis > or =50% in at least one of three major coronary arteries by coronary angiography. The genotypes (determined by polymerase chain reaction) of AGT gene codon 174 were not significantly associated with CAD in the total study population. However, the frequency of T/T homozygotes of AGT codon 174 was significantly higher in CAD patients compared to controls in each of three subgroups: 1) body mass index (BMI) below the median value of 24.1 kg/m2; 2) not more than two CAD risk factors out of five (hypercholesterolemia, hypertension, diabetes mellitus, smoking, and family history of CAD); and 3) the ACE I/I genotype. The M/M genotype of AGT codon 235 was negatively associated, and the ACE D/D genotype was positively associated, with CAD in the total study population. Our results indicate that the T/T genotype of AGT codon 174 may be a risk factor for CAD in Japanese individuals with low BMI, lesser CAD risk factors, or ACE I/I genotype.