This report describes the distribution of serum creatinine levels by sex, age, and ethnic group in a representative sample of the US population. Serum creatinine level was evaluated in the third National Health and Nutrition Examination Survey (NHANES III) in 18,723 participants aged 12 years and older who were examined between 1988 and 1994. Differences in mean serum creatinine levels were compared for subgroups defined by sex, age, and ethnicity (non-Hispanic white, non-Hispanic black, and Mexican-American). The mean serum creatinine value was 0.96 mg/dL for women in the United States and 1.16 mg/dL for men. Overall mean creatinine levels were highest in non-Hispanic blacks (women, 1.01 mg/dL; men, 1.25 mg/dL), lower in non-Hispanic whites (women, 0.97 mg/dL; men, 1.16 mg/dL), and lowest in Mexican-Americans (women, 0.86 mg/dL; men, 1.07 mg/dL). Mean serum creatinine levels increased with age among both men and women in all three ethnic groups, with total US mean levels ranging from 0.88 to 1.10 mg/dL in women and 1.00 to 1.29 mg/dL in men. The highest mean creatinine level was seen in non-Hispanic black men aged 60+ years. In the total US population, creatinine levels of 1.5 mg/dL or greater were seen in 9.74% of men and 1.78% of women. Overall, among the US noninstitutionalized population, 10.9 million people are estimated to have creatinine values of 1.5 mg/dL or greater, 3.0 million have values of 1.7 mg/dL or greater, and 0.8 million have serum creatinine levels of 2.0 mg/dL or greater. Mean serum creatinine values are higher in men, non-Hispanic blacks, and older persons and are lower in Mexican-Americans. In the absence of information on glomerular filtration rate (GFR) or lean body mass, it is not clear to what extent the variability by sex, ethnicity, and age reflects normal physiological differences rather than the presence of kidney disease. Until this information is known, the use of a single cutpoint to define elevated serum creatinine values may be misleading.