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Some evidence suggests that angiotensin-converting enzyme insertion/deletion (I/D) polymorphism may play a role in endothelium-dependent vasodilatation. However, the impact of I/D polymorphism on endogenous nitric oxide production, which may be of great therapeutic significance, has scarcely been studied. This study aimed to investigate this in hypertensives and hypercholesterolaemics. Adult Han subjects were recruited by cluster sampling from two communities in Shunde, Guangdong province, China. Plasma nitrite and nitrate (NO) levels were determined by colorimetry assay and angiotensin II and 6-keto-prostaglandin F1-alpha by radioimmunoassay. Angiotensin-converting enzyme gene I/D polymorphism were genotyped by polymer chain reaction-amplified fragment length polymorphism. Of the 779 subjects who met our inclusion criteria, 502 were with normotensive and normocholesterolaemic, 76 had hypertension only, 146 hypercholesterolaemia only, and 55 had both hypertension and hypercholesterolaemia. Among subjects with hypertension only, the plasma levels of NO for genotype DD were significantly lower than those for genotype II ( P = 0·034). And the plasma levels of NO for genotype DD was significantly higher than those for genotype II ( P = 0·040) in subjects with hypercholesterolaemia only. Our results suggest that I/D polymorphism has an impact on in vivo NO production in hypertensives and hypercholesterolaemics at the population level. Hypertensives with allele D may be benefit from -arginine supplementation and hypercholesterolaemics with allele D may respond better to statins or antioxidants. [ABSTRACT FROM AUTHOR]