The relationship between hyperhomocysteinemia and coronary artery disease (CAD) was investigated and the influence of environmental factors (Folate, VitB12) and genetic factors [N5,N10 methylenetetrahydrofolate reductase gene (MTHFR) or MTHFR gene mutation] on plasma homocysteine (Hcy) levels and the risk of CAD observed. Fifty one CAD patients and 30 CAD free subjects were recruited in the study. The polymorphisms of MTHFR gene were analyzed by PCR RFLP and plasma total Hcy levels were measured by high performance liquid chromatography with fluorescence detection. Plasma folate and vitamin B12 concentrations were measured by an automated chemiluminescence method. It was found that mean total plasma Hcy concentrations were significantly higher in CAD patients than in CAD free subjects ( P <0.01). The differences were also apparent among the three genotypes of MTHFR gene in CAD group ( P <0.05). There was no significant difference in the genotype distributions and allele frequencies between the two groups. A strong inverse correlation was found between folate or vitamin B12 and plasma Hcy levels according to MTHFR genotype ( P <0.01). It was concluded that hyperhomocysteinemia is a new independent risk factor for CAD. However, MTHFR gene mutation alone does not relate significantly to the morbidity of CAD since hyperhomocysteinemia and its influence on the risk of CAD are decided by both environmental and genetic factors. Supplementary treatment with vitamins B can effectively lower the plasma levels of Hcy, thus maybe reduceing the risk of CAD. The relationship between hyperhomocysteinemia and coronary artery disease (CAD) was investigated and the influence of environmental factors (Folate, VitB12) and genetic factors [N5, N10 methylenetetrahydrofolate reductase gene (MTHFR) or MTHFR gene mutation] on plasma homocysteine The risk of CAD observed. Fifty one CAD patients and 30 CAD free subjects were recruited in the study. The polymorphisms of MTHFR gene were analyzed by PCR RFLP and plasma total Hcy levels were measured by high performance liquid chromatography with fluorescence detection. Plasma folate and Vitamin B12 concentrations were measured by an automated chemiluminescence method. It was found that mean total plasma Hcy concentrations were significantly higher in CAD patients than in CAD free subjects (P <0.01). The differences were also apparent among the three genotypes of MTHFR gene in CAD group (P <0.05). There was no significant difference in the genotype distributions and allele freque A was found that folate or vitamin B12 and plasma Hcy levels according to MTHFR genotype (P <0.01). It was therefore that hyperhomocysteinemia is a new independent risk factor for CAD. However, MTHFR gene mutation alone does not relate significantly to the morbidity of CAD since hyperhomocysteinemia and its influence on the risk of CAD are decided by both environmental and genetic factors. Supplementary treatment with vitamins B can effectively lower the plasma levels of Hcy, thus maybe reduceing the risk of CAD .