Pathophysiological processes in coronary artery disease (CAD) are influenced by genetic factors. Since (i) inducible nitric oxide synthase (iNOS) has important cardiovascular effects, and (ii) the promoter of the iNOS gene (NOS2A) is genetically modulated by a 4 bp insertion/deletion (+/-) polymorphism located 0.7 kb upstream, we decided to examine the influence of this variant on clinical variables in 856 CAD patients of Anglo-Celtic/Northern European extraction. We found that 2% of CAD patients were homozygous for the + allele, and 19% were heterozygous. Males made up 74% of the patient group, and in these the + allele was associated with 38% higher plasma glucose levels (P=0.005), a 4.8% elevation in the waist/hip ratio (P=0.009) and a 48% greater frequency of unstable angina (P=0.014). The + allele, by influencing iNOS expression, could thus contribute to indices of insulin resistance and angina severity in male CAD patients.