Cross-cultural epidemiological studies of incident cardiovascular disease in the diabetic patient have demonstrated marked differences in susceptibility that may be due to a genetic factor. The coronary artery collateral circulation is the chief determinant of the size of a myocardial infarction and is highly variable between patients. We recently demonstrated that a functional allelic polymorphism in the haptoglobin gene is correlated with a number of diabetic vascular complications. We thus set out to test the hypothesis that haptoglobin phenotype is associated with collateral formation in the setting of diabetes. We correlated the Hp phenotype (1-1, 2-1 or 2-2) as determined by polyacrylamide electrophoresis with the presence or absence of coronary collaterals by angiography in 82 consecutive diabetic patients and 138 consecutive non-diabetic patients undergoing catheterization. We found that diabetic patients with the Hp phenotype 2-1 were more likely to have collaterals than diabetic patients with the Hp phenotype 2-2 (P=0.007). There was no correlation between Hp phenotypes and the presence of collaterals in non-diabetic patients. Hp phenotype thus appears to be associated with the development of the coronary collateral circulation in diabetic patients with coronary artery disease. Haptoglobin 2-2 may predispose to less compensation for coronary artery stenosis in diabetic patients, and thereby portend a worse prognosis.