BACKGROUND: Lean mass and resting energy expenditure (REE) decrease with age. However, it is unknown whether age-related changes in regional lean and fat mass are responsible for the age-related decrease in REE. OBJECTIVE: Our objective was to determine how regional lean and fat mass vary with age and whether age is independently related to REE after adjustment for regional fat and lean mass. DESIGN: The study was a cross-sectional evaluation of 58 white women aged 23-77 y. Regional and whole-body lean and fat mass were measured by dual-energy X-ray absorptiometry, subcutaneous abdominal tissue (SAT) and intraabdominal adipose tissue (IAF) by computed tomography, and REE by ventilated-canopy indirect calorimetry. RESULTS: Independent of other significant correlates, age was significantly and independently associated with greater IAF (beta = 0.49) and less leg lean mass (beta = -0.35). IAF (r = -0.28) and IAF:SAT (r = -0.31) correlated negatively with REE. REE was negatively associated with greater age (beta = -0.42), independent of changes in lean and fat mass in different parts of the body. By contrast, trunk lean (beta = 0.27) and leg fat (beta = 0.27) mass were associated with greater REE independent of age and other body-composition variables. CONCLUSIONS: These results suggest that trunk lean mass (presumably primarily organ tissue) is relatively resistant to age-related changes in body composition, whereas muscle mass, especially leg muscle, tends to be lost. These data also suggest that the age-related decreases in REE are not fully explained by changes in body composition.