Genetic and environmental influences on muscle circumference measurements of the extremities were estimated in 105 pairs of twins between 10 and 14 yr of age. Four circumferences, extended upper arm (EAC), forearm (FC), thigh (TC), and calf (CC), were measured. Univariate model fitting revealed that the largest part (87-95%) of the variance for all circumferences at most ages was explained by additive genetic factors. Sex differences were observed for some age categories. Multivariate analyses showed a different pattern evolving according to age and gender. In boys from 10 to 12 yr of age, one general genetic factor influenced all four circumferences. With increasing age, an arm-leg model emerged, one genetic factor influencing the arm and another genetic factor the leg circumferences. In young girls one genetic factor loaded on the proximal (EAC, TC) and another on the distal (FC, CC) circumferences. With subjects at age 14 yr, an arm-leg model was observed. High genetic correlations indicated that genetic factors related to EAC, FC, TC, and CC did not act independently. The age-and gender-specific changes in the genetic structure suggest pubertal influences. This study shows that muscle circumferences are highly heritable characteristics and are therefore a promising starting point at which to locate their genes. Gene mapping could validate the gender-specific change of the genetic structure with age and region.