The aim of this study was to critically examine the influence of body size on maximal oxygen uptake (VO2 max) in boys and men using body mass (BM), estimated fat free mass (FFM), and estimated lower leg muscle volume (VOL) as the separate scaling variables. VO2 max and an in-vivo measurement of VOL were assessed in 15 boys and 14 men. The FFM was estimated after percentage body fat had been predicted from population specific skinfold measurements. Using nonlinear allometric modeling, common body size exponents for BM, FFM, and VOL were calculated. The point estimates for the size exponent (95% CI) from the separate allometric models were: BM 0.79 (0.53 to 1.06), FFM 1.00 (0.78 to 1.22), and VOL 0.64 (0.40 to 0.88). For the boys, substantial residual size correlations were observed for VO2 max/BM(0.79) and VO2 max/FFM(1.00), indicating that these variables did not correctly partition out the influence of body size. In contrast, scaling by VOL(0.64) led to no residual size correlation in boys or men. Scaling by BM is confounded by heterogeneity of body composition, and potentially substantial differences in the mass exponent between boys and men. The FFM is precluded as an index of involved musculature because VOL did not represent a constant proportion of FFM (VOL proportional to FFM(1.45) (95% CI, 1.13 to 1.77) in the boys (unlike the men). We conclude that VOL, as an indicator of the involved muscle mass, is the most valid allometric denominator for the scaling of VO2 max in a sample of boys and men heterogeneous for body size and composition.