Hyperhomocysteinemia is a well-known independent risk factor for cardiovascular disease and is a prevalent abnormality in chronic renal failure. However, studies on this abnormality in children with chronic renal failure, before renal replacement therapy, are scarce. In this study, we measured the plasma homocysteine levels of 27 children (mean age 8.9+/-4.8 years) with predialytic chronic renal failure, and analyzed the effect of folic acid supplementation (1 mg daily for 4 weeks) on the homocysteine levels in 14 of these children. The baseline homocysteine concentration of the patients (12.5+/-6.0 micro mol/l) was higher than that of the control group (5.9+/-1.8 micro mol/l, P<0.001), and correlated positively with age and negatively with folic acid concentration. Folic acid and vitamin B(12) concentrations were not below normal in any patient. The homocysteine concentration was decreased from 13.2+/-6.6 micro mol/l (pretreatment) to 9.3+/-4.2 micro mol/l by folic acid supplementation in the 14 patients. Folic acid supplementation also lowered the prevalence of hyperhomocysteinemia from 64.3% to 42.9%. According to these results, we recommend that folic acid supplementation be started in children with chronic renal failure early in the disease course.