This study examined gender differences in resting metabolic rate (RMR) across a broad age spectrum after controlling for differences in body composition and aerobic fitness. Three hundred twenty-eight healthy men (17-80 yr) and 194 women (18-81 yr) volunteers were characterized for RMR, body composition, physical activity, peak oxygen consumption (peak VO2), anthropometrics, and energy intake. Measured RMR was 23% higher (P < 0.01) in men (1,740 +/- 194 kcal/day) than in women (1,348 +/- 125 kcal/day). Multiple regression analysis showed that 84% of individual variation in RMR was explained by fat-free mass, fat mass, peak VO2, and gender. After controlling for differences in fat-free mass, fat mass, and peak VO2, a lower RMR (3%; P < 0.01) persisted in women (1,563 +/- 153 kcal/day) compared with men (1,613 +/- 127 kcal/day). Adjusted RMR in premenopausal (P < 0.01) and postmenopausal (P < 0.05) women was lower than in men of a similar age. Our results support a lower RMR in women than in men that is independent of differences in body composition and aerobic fitness.