Background/Aims: Vascular diseases are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients and they cannot be explained entirely by the prevalence of traditional risk factors for atherosclerosis. The role of hyperhomocysteinemia as an additional risk factor in the development of accelerated atherosclerosis and/or thrombosis in these patients has been suggested possibly due to homocysteine (Hcy) induced endothelial cell injury. This study was aimed at evaluation of the Hcy status in children with chronic renal failure (CRF) especially in those suffering from ESRD and the possible role of folic acid and vitamin B<sub>12</sub> therapy in the correction of hyperhomocysteinemia if present. Methods: This study included 40 patients with CRF, 30 on regular hemodialysis (HD) treatment (group I) and 10 on conservative (medical) treatment (group II) in comparison to 20 healthy age- and sex-matched controls (group III). The basal serum levels of Hcy, folic acid and vitamin B<sub>12</sub> as well as plasma level of activated protein C resistance (APC-R) were measured in patients and controls. Results: The mean serum Hcy was significantly higher in those on regular HD (17.9 ± 10.07 µmol/l) in comparison to those on conservative treatment (8.05 ± 2.99 µmol/l) (p < 0.001) and controls (7.07 ± 2.24 µmol/l) (p < 0.001), while there was no significant variation between the latter two groups. The mean values of APC-R, folic acid and vitamin B<sub>12</sub> failed to show any significant difference in the three studied groups. No significant difference in the basal Hcy level between patients with previous history of vaso-occlusive disease and those without was found. Half of the patients on regular HD (group Ia) (n = 15) were given folic acid as 50 mg of 5-formyl-tetrahydrofolate (the active form of folic acid) intravenously once weekly after the dialysis session for 4 weeks. The other half (group Ib) (n = 15) received in addition to folic acid therapy, vitamin B<sub>12</sub> 1,000 µg hydroxycobalamine once intramuscularly. After therapy the mean Hcy decreased significantly in those who received folic acid and vitamin B<sub>12</sub> (7.80 ± 3.77 µmol/l) (p < 0.001) to a level comparable to the basal levels in conservative and control groups, whereas a non-significant decrease was found in those who received folic acid only (13.3 ± 11.47 µmol/l) (p > 0.05). Conclusions: Hcy is high in children with ESRD on regular HD and combined therapy of the active form of folic acid and vitamin B<sub>12</sub> is of value in decreasing Hcy values comparable to that in controls.