Background and objectives: The objective of this study was to describe the normal range of serum cystatin C and identify factors associated with variability in serum cystatin C contrasting with factors that are known to influence creatinine levels in the general US adolescent population.Design, setting, participants, & measurements: Serum cystatin C and creatinine were measured in 719 participants aged 12 to 19 yr in the Third National Health and Nutrition Examination Survey, a national cross-sectional survey conducted in 1988 through 1994. We calculated gender-and race/ethnicity-specific cystatin C and creatinine ranges and conducted multivariable linear regression analyses to assess factors that contribute to variability in cystatin C and creatinine levels.Results: Overall, the mean serum cystatin C level was 0.84 mg/L and was higher in male than female individuals and higher in non-Hispanic white versus non-Hispanic black and Mexican American individuals. The mean serum creatinine was 0.71 mg/dl and was higher in male than in female individuals but lower in non-Hispanic white and Mexican American compared with non-Hispanic black individuals. Unlike creatinine, which increases with age from 12 to 19 yr, cystatin C levels decrease, particularly in female individuals. After adjustment for age, gender, and race/ethnicity, uric acid and blood urea nitrogen were significantly associated with cystatin C levels.Conclusions: Serum cystatin C is significantly related to gender, age, race/ethnicity, uric acid, and blood urea nitrogen in adolescents.