Athletes participating in unilateral dominant sports are useful models for investigating skeletal responses to mechanical loading as they provide controlled evidence in the absence of completing a randomized controlled trial. Throwing athletes may be an additional model for this purpose as they overload their dominant upper extremity enabling the contralateral side to act as an internal control and load the bones of the upper extremity purely via the generation of internal (i.e. muscular) forces without superposition of externally applied loads (i.e. impact with an external object). The aim of this study was to investigate upper extremity bone adaptation in throwing athletes and explore factors that predict this adaptation. Two cohorts were recruited-male baseball players (throwers; n=15) and matched controls (controls; n=15). Each subject was assessed for shoulder range and strength, and upper extremity bone mass, structure and estimated strength. Throwers had substantially greater skeletal differences between their dominant and nondominant upper extremities than controls, indicating that throwing induces greater adaptation than induced by habitual loading of the dominant upper extremity. Bone adaptation in throwers was localized to the humerus, with the midshaft humerus in the dominant upper extremity of throwers having enhanced bone mass, structure and estimated strength. The largest effect was for estimated strength of the midshaft humerus which had 30% greater polar moment of inertia (I(P)) in throwers and suggests adaptation to resist torsional loads. The skeletal effect of throwing at the midshaft humerus was influenced by playing position with pitchers and catchers displaying greater dominant-to-nondominant differences than fielders, and was predicted by years throwing and dominant-to-nondominant difference in upper arm lean cross-sectional area. The latter two variables explained 67% of the variance in dominant-to-nondominant differences in I(P). Collectively, these data indicate that throwing induces substantial adaptation within the midshaft humerus. Adaptation was primarily in the direction of torsion which is consistent with biomechanical and injury data suggesting throwing introduces high magnitude torsional forces. As the magnitude of adaptation in throwers was equivalent to that observed in athletes participating in other unilateral dominant sports, throwers represent an alternative model for investigating the skeletal effects of mechanical loading.