A common mutation (C677-->T) in methylenetetrahydrofolate (MTHFR) gene, involved in the metabolism of homocysteine, has been suggested to play a role in increasing cardiovascular disease risk. We determined the frequency of C677-->T genotypes and alleles in 155 Caucasian patients with angiographically documented coronary artery disease (CAD) and in 155 age and sex matched normal Caucasian individuals. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI and gel electrophoresis. The distribution of MTHFR C677-->T genotypes followed the Hardy-Weinberg equilibrium. The distribution of MTHFR genotypes and the frequency of alleles were similar in cases and controls. The TT genotype was present in 8% of controls as compared to 6% of cases (P = 0.50, OR = 0.82; 95% CI: 0.34-1.96). The frequency of T allele was also similar in patients with CAD compared with controls (0.29 vs. 0.33; P = 0.29). There was also no significant association between C677-->T genotypes and the risk of myocardial infarction. In a subgroup of 44 cases and 89 controls who had no conventional risk factors for CAD (hyperlipidemia, hypertension, diabetes mellitus, and smoking), the frequency of TT genotype was similar (11% vs. 8%, respectively, P = 0.71, OR: 0.67, 95% CI: 0.20-2.23). Thus, the MTHFR TT genotype is not a major genetic risk factor for predisposition to CAD and its thrombotic complications in this population.