We determined the sensitivity, specificity, receiver operating characteristics and correlation between. cystatin C (cysC) and two widely used markers of renal function, creatinine clearance and serum creatinine, in 244 patients (84 diabetics, 84 hypertensive an 76 healthy subjects). Renal failure was defined as creatinine clearance of less than either 80 or 60 mL/min. Variables were evaluated for two definitions of renal failure and compared between patient groups. Correlation coefficients with cysC were -0.87 for creatinine clearance and 0.92 for creatinine in patients with hypertension; - 0.90 for creatinine clearance and 0.97 for creatinine in diabetics; and -0.61 for creatinine clearance and 0.94 for creatinine in the control group. The receiver operating characteristic curves with a cut-off value of 60 mL/min were similar for creatinine and cysC, while at 80 mL/min they were 0.626 for creatinine and 0.813 for cysC levels. We classified the patients into three groups with respect to creatinine clearance (1, > 80 mL/min; 2, 60-80 mL/min; 3, < 60 mL/min). Mean creatinine (p < 0.0001) and cysC (p < 0.0001) levels were significantly different between all the groups. Sensitivity, specificity and predictive values were higher for cysC levels, particularly in diabetics and hypertensive patients. The current study suggests that cysC is preferable for detecting temporal changes in renal function in the early stages of renal insufficiency.