Homocysteine (HMC) is a sulfur containing amino acid, which plays a role in methionine metabolism. Folic acid (FA) and vitamin B12 (B12) are essential for remethylization of HMC to methionine. HMC level increases in the deficiency of these vitamins. Hyperhomocysteinemia causes vascular endothelial damage, which causes atherosclerosis. The aim of this study is to investigate the effect of valproate (VA) and carbamazepine (CBZ) on the serum levels of HMC, B12, and FA.Thirty-six children receiving CBZ and 30 children receiving VA for epilepsy for the last 1-year period and 29 healthy children as control were the population of this study. After 6 h of fasting serum HMC, B12, and FA levels were measured and results were compared statistically. Mean values of HMC, FA, and B12 levels in control group were 9.2+/-2.7 micromol/l, 9.0+/-2.0 ng/ml, and 342+/-162 pg/ml, in VA group 14.0+/-6.8 micromol/l, 7.3+/-2.9 ng/ml, and 368+/-159 pg/ml, in CBZ group 16.0+/-13.1 micromol/l, 7.5+/-3.3 ng/ml, and 285+/-158 pg/ml, respectively. Serum HMC levels were higher in VA and CBZ groups than control group (P<0.01 and P<0.05, respectively). Serum FA levels were lower in VA and CBZ groups compared to control group (P<0.05). Serum levels of B12 were not different between VA and control groups (P>0.05). In CBZ group serum B12 levels were lower than control group (P<0.05).FA may be added to the treatment protocol (if the patients take only CBZ, then B12 should also be added) for patients taking these antiepileptic drugs to decrease the degenerative effect of VA and CBZ on vascular endothelium.