Serum cystatin C is a novel marker of renal function claimed to be superior to plasma creatinine. We assessed both parameters in young normotensive subjects (n = 12; 6 men; mean age, 25 ± 2 years) and elderly normotensive and hypertensive subjects (n = 41; 19 men; mean age, 67 ± 6 years). Glomerular filtration rate (GFR) was measured in all individuals using the inulin clearance (Cln) technique. Compared with young subjects, mean GFR was modestly but significantly (P<0.001) less in elderly subjects (young, 119 ± 11 mLmin/1.73 m2 versus elderly, 104 ± 12 mL/min/1.73 m2). Mean plasma creatinine concentration was identical in both groups (young, 0.93 ± 0.11 mg/dL versus elderly, 0.93 ± 0.10 mg/dL; P<0.90). Mean serum cystatin C concentration was significantly (P<0.001) greater in elderly subjects (0.84 ± 0.10 mg/L) compared with young subjects (0.69 ± 0.08 mg/L). In all but one elderly subject, plasma creatinine concentration was within the 95% confidence interval of plasma creatinine concentration in young subjects. Eleven of 41 elderly subjects (27%) had GFRs less than the lower 95% confidence interval, respectively, and 12 of 41 elderly subjects (29%) had a serum cystatin C concentration greater than the upper 95% confidence interval in young subjects. The correlation between serum cystatin C concentration and Cln (r = -0.65; P<0.001) was considerably better than between plasma creatinine concentration and Cln (r = -0.30; P<0.02). Serum cystatin C concentration is a better marker of renal dysfunction (ie, reduced GFR) than plasma creatinine concentration, at least in elderly subjects with plasma creatinine concentrations within the normal range.