We have determined the prevalence of hyperhomocysteinemia and tested its relationship with coronary heart disease in Tunisian patients. The study included 70 angiogrphically proven coronary patients and 140 age- and sex-matched healthy subjects. Plasma homocysteine folate and vitamin B12 were analyzed by immunoenzymatic methods. Hyperhomocysteinemia was considered for plasma homocysteine concentration >17 micromol/L. Mean plasma homocysteine concentration and hyperhomocysteinemia prevalence were significantly (p<0.001) higher in patients (16.3 +/- 7.9 micromol/L and 29%) than controls (12.6 +/- 4.0 micromol/L and 10%). The association between hyperhomocysteinemia and coronary heart disease persisted after adjusting on main cardiovascular risk factors (multi adjusted odds ratio, 2.99; 95% CI, 1.18-7.59; p=0.02). No association was observed between hyperhomocysteinemia and coronary disease severity and extent. This study showed an independent association between hyperhomocysteinemia and coronary heart disease, suggesting a role of hyperhomocysteinemia in atherothrombogenesis. However, causal relationship is not yet established. Until results of homocysteine-lowering therapy trials become available, hyperhomocysteinemia should be researched and treated in coronary heart disease patients.