This study attempts to clarify the characteristics of renal tubular damage in preterm infants with renal failure. Sixty-one neonates (17 term and 44 preterm infants) were divided into three groups: 15 infants with intrinsic renal failure (IRF), five term and 10 preterm; 19 with pre-renal renal failure (PRF), five term and 14 preterm; and 27 without renal dysfunction (control), seven term and 20 preterm. Urine was collected for an 8 h period on the 2nd or 3rd day of life to determine the following parameters: creatinine clearance (Ccr), fractional excretion of sodium (FENa), urinary N-acetyl-beta-D-glucosaminidase (NAG) index and endothelin-1 (ET-1) excretion. Parameters of renal tubular function and/or renal tubular damage such as FENa, NAG index and ET-1 excretion were considered as a useful marker to differentiate IRF from PRF in preterm infants. However, these parameters were significantly elevated in preterm infants with PRF. These findings led us to make the following speculations: (i) renal tubular damage may easily occur in preterm infants; and (ii) there still remains difficulty in differentiation between IRF and PRF using Ccr instead of the fluid challenge test.