The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r = -0.70, p < 0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-1-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.