To evaluate the efficacy of supplementation with high dose folic acid with and without vitamin B 12 in lowering plasma total homocysteine (tHcy) concentrations in hemodialysis (HD) patients, we studied 36 HD patients randomized into four groups according to the received therapeutic regimen: group I (only folic acid (FA), 5 mg/day), group II (FA, 5 mg/day + vitamin B 12 , 1 mg/day) group III (only FA, 15 mg/day), group IV (FA, 15 mg/day, vitamin B 12 , 1 mg/day) for a period of 8 weeks. Plasma tHcy and serum FA and vitamin B 12 levels were measured at baseline and after the supplementation period. Dietary intakes were assessed during the study period. At baseline, 27.8% of the patients had normal levels of tHcy and 72.2% had hyperhomocysteinemia. After supplementation, plasma tHcy increased by 1.35% in group I and decreased by 6.99%, 14.54% and 30.09% in groups II, III and IV respectively, which was only significant in group IV (P= 0.014). The patients did not show any significant changes in serum folic acid, but a significant change in serum vitamin B 12 in group IV (P= 0.006). Percentage of patients reaching normal levels of plasma tHcy was 5.6 fold higher in group IV than in the reference group (group I). No correlations were found between changes of plasma tHcy levels and dietary intakes. We conclude that oral supplementation with 15 mg/day folic acid together with 1 mg/day of vitamin B 12 is effective in reducing tHcy levels in HD patients. These supplements also have a desirable effect on serum folic acid and vitamin B12.