Cystatin C (CysC) is a low-molecular-mass protein (13,343 dalton, 120 amino acids) belonging to the cystatin superfamily of reversible inhibitors of cysteine proteases. CysC appears to be eliminated from the circulation almost exclusively by glomerular filtration, which makes it a promising endogenous marker of renal function. CysC has been demonstrated to reflect glomerular filtration rate better than other low-molecular-weight proteins, including creatinine (Cr). We established reference values for serum CysC and compared them with Cr in 108 preterm infants by particle-enhanced nephelometric immunoassay. On the first day, serum CysC values ranged from 1.25 to 2.84 mg/L, significantly decreasing after 3 days of life. Cr levels determined simultaneously on the first day ranged from 0.05 to 1.12 mg/dl and were also significantly different from day 3 levels. Both CysC and Cr levels were independent of gender, birth weight, hemoglobin levels, and hydration state. Cr correlated negatively with gestational age (r=-0.25, p=0.009), but not CysC. A significant correlation was found between CysC and Cr on day 1 (r=0.21, p=0.031), but no correlation was found according to day 3 blood samples (r=0.19, p=0.053). CysC is regarded as an alternative for assessing renal function in preterm neonates, but its advantages over Cr are not yet proven.