Objective. To study a role of MTHFR mutations and their associations with the disturbances of basic parameters of the folate cycle in the development of ischemic stroke (IS). Material and methods. Fifty-one post-stroke patients, 26 women and 25 men, aged from 29 to 87 years, were included in the study. The control group consisted of 47 healthy people, 23 women and 24 men, aged from 30 to 83 years. MTHFR: rs1801131 and rs1801133 polymorphisms were genotyped. Contents of folate, B12 and homocysteine were measured. Results. The risk group which was characterized by the presence of risk variants of rs1801131 and rs1801133 polymorphisms, changes in the parameters of the folate cycle (the decrease in B12 concentration (≤500 pg/ml)) in the combination with hyperhomocysteinemia (≥13 mcmol/L) was identified. Conclusion. The disturbance of the folate cycle, including gene variations, is a basic pathogenetic link in the development of cerebral atherosclerosis and associated cerebrovascular diseases.