The relationship between fat-free mass (FFM) and resting metabolic rate (RMR) was compared in young men (n = 24; age 18-33 yr), old men (n = 24; 69-89 yr), and old women (n = 20; 67-75 yr). Body composition was assessed using anthropometry, bioelectrical impedance analysis (BIA), and isotope dilution with 18O-labeled water. RMR was measured at least twice using an open-circuit indirect calorimetry system with a ventilated hood. The results indicate that the different methods for assessing body composition vary substantially and should not be used interchangeably. Anthropometry was not adequate to assess group differences in body fatness, although skinfold measures may be appropriate for within-group comparisons. BIA correlated well with the isotope-dilution technique and may be a useful measure of FFM. Finally, RMR was lower in the old men than the young (1.04 +/- 0.02 vs. 1.24 +/- 0.03 kcal/min, P less than 0.001) and remained lower even when adjusted for FFM estimated by isotope dilution (P less than 0.001). RMR in the women was also lower (0.84 +/- 0.02 kcal/min), but in contrast to the difference between young and old men, RMR adjusted for FFM did not differ (P = 0.16) between old men and women. Therefore, it is clear that differences in FFM cannot fully account for the lower RMR in the old, suggesting that aging is associated with an alteration in tissue energy metabolism.