To investigate the relation between plasma homocysteine (Hcy) and cerebral ischemic diseases and that between polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and cerebral ischemic diseases.The plasma homocysteine (Hcy) and genetic polymorphism of MTHFR among forty-nine cases with ischemic cerebral diseases, including 25 with acute cerebral infarction (CI) and 25 with transient ischemic attacks (TIA), were investigated. Fifty-five age- and sex-matched healthy persons were used as controls. All the subjects underwent brain CT, carotid duplex, transcranial Doppler examination, plasma Vitamin B(12) and folic acid examination, besides examination of plasma Hcy and nucleotide 677 MTHFR genotypes. The effects of age, liver function, renal function, smoking, drinking, plasma vitamin B(12), and folic acid were analyzed.The mean plasma Hcy was significantly higher in the CI group and TIA group (17.4 +/- 7.6 micromol/L and 16.6 +/- 5.2 micromol/L) compared with that in the control group (12.6 +/- 5.2 micromol/L, P 0.05). The difference of Hcy was significant between those being T/T homozygotic and those not being T/T homozygotic in different groups. There was no statistical correlation between plasma Hcy level and extra- and intracranial stenosis of cerebral artery. Increase of BUN and smoking were significantly correlated with increase of Hcy (P < 0.05). The concentrations of plasma Vitamin B(12) and folic acid were significantly correlated with that of Hcy.Homozygote of mutant MTHFR gene C677T causes hyperhomocystinemia. There is a significantly association between hyperhomocystinemia and ischemic cerebrovascular disease. The frequency of mutation in MTHFR genotype is higher in Chinese than in Caucasians. In addition to gene mutation, renal function and smoking are related to increase of plasma Hcy. No correlation between genotype of MTHFR and stroke is found.