Resting metabolic rate is an important predictor of obesity and is closely related to fat-free mass. There is evidence that fat-free mass may be partly determined during critical periods of growth before and after birth. The objective of this study was to examine the relationship between size at birth, childhood growth and fat-free mass and resting metabolic rate in adult life. 318 men and women with detailed records of body size at birth and growth during school years participated in the study. Fat-free mass correlated positively with birth weight among both sexes (r = 0.264, p < 0.001). Those having a higher birth weight had a higher fat-free mass at any adult BMI. Fat-free mass among men increased by 2.2 kg (95 % Cl 0.5 to 3.9; p = 0.01) for every kg increase in birth weight and by 1.5 kg (95 % Cl 1.3 to 1.7, p < 0.0001) for every kg/m(2) BMI in adult life. In women, fat-free mass increased by 2.7 kg (95 % Cl 1.6 - 3.9; p < 0.001) for every kg increase in birth weight and by 0.8 kg (95 % CI 0.7 to 1.0, p < 0.001) for every kg/m(2) of BMI in adult life. Height, weight and body mass index at each age from 7 to 15 years were also strongly, positively associated with fat-free mass. A negative correlation between birth weight and resting metabolic rate expressed per unit of fat-free mass (r = - 0.158; p < 0.001) was found. Fat-free mass may be determined during critical periods of muscle growth in utero and during childhood. The muscle tissue of people who had a lower birth weight is more metabolically active than those with a higher birth weight. This may protect them from the increased risk of obesity associated with low fat-free mass.