We previously derived a cellular level approach for a whole-body resting energy expenditure (REE) prediction model by using organ and tissue mass measured by magnetic resonance imaging (MRI) combined with their individual cellularity and assumed stable-specific resting metabolic rates. Although this approach predicts REE well in both young and elderly adults, there were no studies in adolescents that specifically evaluated REE in relation to organ-tissue mass. It is unclear whether the approach can be applied to rapidly growing adolescents. The aim of the present study was to evaluate the applicability of the previous developed REE prediction model in adolescents, and to compare its applicability in young and elderly adults. Specifically, we tested the hypothesis that measured REE can be predicted from a combination of individual organ and tissue mass and their related cellularity. This was a 2-year longitudinal investigation. Twenty healthy male subjects with a mean age of 14.7 years had REE, organ and tissue mass, body cell mass, and fat-free mass (FFM) measured by indirect calorimetry, whole-body MRI, whole-body (40)K counting and dual-energy X-ray absorptiometry, respectively. The predicted REE (REEp; mean +/- SD, 1,487 +/- 238 kcal/day) was correlated with the measured REE (REEm, 1,606 +/- 237 kcal/day, r = 0.76, P < 0.001). The mean difference (118 +/- 165 kcal/day) between REEm and REEp was significant (P = 0.0047), accounting for 7.3% of REEm for the entire group. The present study, the first of its type in adolescents, does not support the applicability of the organ-tissue-based REE prediction model during rapid adolescent growth. A modified general REE prediction model is thus suggested which may account for the higher REE/FFM ratio observed in adolescents.