There is continuing interest in the link between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and cardiovascular diseases. Studies on various ethnic populations have shown conflicting evidence as to the association of the DD genotype with an increased risk of myocardial infarction. We examined the relationship between various cardiovascular hormones and ACE gene polymorphism in 149 subjects who underwent cardiac catheterization and had normal cardiac function. The distribution of the II, ID, and DD genotypes was 68, 67, and 14, respectively. Although serum ACE activity was higher in DD and ID than in II (II 9.7+/-0.5 IU/l, ID 12.2+/-0.5, DD 12.8+/-1.2; p < 0.005), other factors of the renin-angiotensin system such as plasma renin activity and plasma concentrations of angiotensin II and aldosterone were not different among the three genotypes. Plasma catecholamines did not differ among the ACE genotypes either, however, plasma atrial natriuretic peptide (ANP) was significantly lower in the subjects carrying the D allele (II 38+/-5 pg/ml, ID 26+/-2, DD 21+/-3; p < 0.05). In particular, the DD genotype showed a low plasma ANP level although the left ventricular mass index was greater than the other genotypes (II 133+/-5 g/m2, ID 137+/-6, DD 165+/-7; p < 0.05). The low plasma ANP in the DD genotype may contribute to the increased risk of cardiovascular diseases.