OBJECTIVE: To study the relationship of fat mass, extracellular-to-intracellular-water ratio, and bone mineral density with growth hormone function and physical activity in Prader-Willi syndrome. STUDY DESIGN: There were 17 patients with PWS (10 women, ages 7.5-19.8 years) and 17 obese control patients, matched for gender and bone age. FM and extracellular-to-intracellular-water ratio were measured by bromide-deuterium dilution, BMD by dual-energy x-ray absorptiometry, GH function by fasted serum insulin-like growth factor-I concentration, and physical activity by doubly-labeled water in combination with basal metabolic rate by a ventilated hood. RESULTS: The PWS group had a similar fat mass, but a lower fat-free mass, whereas the extracellular-to-intracellular-water ratio was higher compared with the control group (0.87 +/- 0.07 l/l and 0.80 +/- 0.06 l/l, respectively [P <.01]). Fat mass was inversely related with PA in the PWS group, whereas IGF-I was positively correlated with FFM, ICW, and BMD of the limbs. BMD tended to be lower in patients with PWS. CONCLUSIONS: In children and adolescents with PWS, adiposity is associated with a reduced fat-free mass and extracellular-to-intracellular-water ratio is increased. Both findings are related to GH function and physical activity. BMD, especially in the limbs, tends to be reduced in patients with PWS and is related to GH function.