E levated HDL-cholesterol (C) and apo AI are associated with decreased coronary artery disease (CAD) risk. We determined distributions of two MspI polymorphisms of the apo AI gene, associated in other studies with increased HDL-C, among 644 patients aged < or = 65 years in relation to circulating lipids and CAD severity assessed angiographically. The rare allele distributions at both sites were in Hardy-Weinberg equilibrium in these patients but the base changes were not associated with HDL-C and apo AI levels. However, patients homozygous for the -75 bp substitution were more likely to have one or more significantly diseased vessels (> 50% luminal obstruction)(OR: 4.75, 95%CI: 1.10- 20.46) as also were patients with the rare +83 bp alleles (OR: 2.56, 95%CI: 1.13-5.81). While there was an additive effect of the two polymorphisms to have severe CAD (OR: 6.33, 95%CI: 1.33-30.02), the polymorphism at +83 bp remained significant in predicting CAD severity after adjusting for other variables in a logistic regression analysis (OR: 2.95, 95%CI: 1.26-6.90), which was also strongly associated with the positive family CAD history (P = 0.009). We conclude that patients with these base changes in this Australian coronary population do not have increased HDL-C and apo AI levels but do have more severe CAD.