Many studies have demonstrated a strong association between elevated plasma total homocysteine (tHcys) levels and vascular disease. The aim of the present study was to determine the plasma levels of tHcys in pediatric recipients of renal transplants, to establish possible correlations with renal function, lipid profile, and folate and vitamin B12 status, and to assess whether the C677T and A1298C polymorphisms in the 5, l0-methylenetetrahydrofolate reductase (MTHFR) gene were associated with a particular risk. A total of 26 transplanted children and adolescents were investigated. tHcys levels were elevated in transplanted patients (12.9+/-4.8 micro mol/l) and 73% of these displayed values above the 97th percentile of healthy children. Plasma tHcys correlated negatively with creatinine clearance ( r=-0.58, P<0.001) and plasma vitamin B(12) ( r=-0.40, P<0.05) and positively with plasma triglycerides ( r=0.53, P<0.005). No significant correlations were found between plasma tHcys level and age, gender, time elapsed after transplantation and plasma values of glucose, insulin, folic acid, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, apolipoprotein B, and apolipoprotein A-1. Plasma tHcys level was clearly increased in 3 patients with a MTHFR 677TT/1298AA genotype. In a multiple stepwise regression model plasma creatinine and triglyceride levels and MTHFR 677TT/1298 AA genotype accounted for 60% of the observed plasma tHcys variability. The MTHFR 677CT/1298 AC genotype was not a significant predictor of tHcys plasma levels. We conclude that a moderate degree of hyperhomocysteinemia is often present in renal transplant children and that folate supplementation must be considered in this population.