BACKGROUND: Serum cystatin C has been suggested to be a better marker for GFR than creatinine because believed to be produced at a constant rate by most nucleated cells, and eliminated exclusively by glomerular filtration We compared serum cystatin C with creatinine-based estimates, especially in patients with old age or extreme protein composition to investigate the utility of cystatin C and to identify factors that influence on cystatin C other than renal function. METHODS: A total of 446 patients, admitted to department of nephrology of Korea University Anam Hospital From September 2003 to March 2004, had their glomerular filtration rate (GFR) estimated by DTPA scintigraphy, clearance of creatinine, and calculated from Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) formula. A body composition, the serum creatinine and cystatin C levels were also measured. RESULTS: Serum cystatin C showed similar correlation with DTPA GFR to serum creatinine. The formula, GFR (mL/min/1.73m2) = 61.84 x cystatin C(-0.8135), was derived with better precision than either Cockcroft-Gault or MDRD. The diagnostic accuracy of cystatin C was not better than creatinine in older patients as well as those with overweight, or an extreme protein composition. The addition of age, body surface area, and gender increased the R2 for both serum creatinine and cystatin C. CONCLUSION: Serum cystatin C is a good marker for GFR, but not superior to serum creatinine even in patients with old age, overweight, or an extreme protein composition, and affected by age, body surface area, and gender independent on renal function.