For addressing the influence of muscle mass on serum and urinary creatinine and serum cystatin C, body composition was assessed by skinfold thickness measurement and bioelectrical impedance analyses. A total of 170 healthy individuals (92 women, 78 men) were classified as sedentary or with mild or moderate/intense physical activity. Blood, 24-h urine samples, and 24-h food recall were obtained from all individuals. Serum and urinary creatinine correlated significantly with body weight, but the level of correlation with lean mass was even greater. There was no significant correlation between body weight and lean mass with cystatin C. Individuals with moderate/intense physical activity presented significantly lower mean body mass index (23.1 +/- 2.5 versus 25.7 +/- 3.9 kg/m(2)) and higher lean mass (55.3 +/- 10.0 versus 48.5 +/- 10.4%), serum creatinine (1.04 +/- 0.12 versus 0.95 +/- 0.17 mg/dl), urinary creatinine (1437 +/- 471 versus 1231 +/- 430 mg/24 h), protein intake (1.4 +/- 0.6 versus 1.1 +/- 0.6 g/kg per d), and meat intake (0.7 +/- 0.3 versus 0.5 +/- 0.4 g/kg per d) than the sedentary individuals. Conversely, mean serum cystatin did not differ between these two groups. A multivariate analysis of covariance showed that lean mass was significantly related to serum and urinary creatinine but not with cystatin, even after adjustment for protein/meat intake and physical activity. Cystatin C may represent a more adequate alternative to assess renal function in individuals with higher muscle mass when mild kidney impairment is suspected.