The best predictor of energy expenditure in man is the fat-free mass of the body. Fat-free mass explains most of the variation in resting metabolic rate and even in total metabolic rate under sedentary conditions. We studied possible determinants of fat-free mass as routes to influence energy metabolism. Existing data sets were analysed with observations on height, fat mass (FM), fat-free mass (FFM), and habitual level of physical activity (PA). PA was calculated from average daily metabolic rate (ADMR) as measured over 1-4-week intervals with 2H2(18)O and basal metabolic rate (BMR): PA = ADMR/BMR. Ninety-six subjects, 66 females and 30 males, from 7 different studies were included. FFM and FM were adjusted for height by taking its ratio to the square of height, in analogy with the body mass index. Subsequently, all analyses were corrected for origin of the data. In a regression analysis FM explained 53 and 40% of the variation in FFM in females and males, respectively. Adding PA to the model raised the explained variation in FFM in females to 62%. In contrast with females (r = 0.10, n.s.), there was an independent relationship between PA and FM in males (r = -0.41, p less than or equal to 0.05), such that a higher PA was related to a lower FM. In conclusion, FFM is a function of FM and PA. The absence of an effect of exercise training on FFM, i.e. additional exercise in weight-reduction programmes, is discussed.