Hu X, Murray WM, Perreault EJ. Muscle short-range stiffness can be used to estimate the endpoint stiffness of the human arm. J Neurophysiol 105: 1633-1641, 2011. First published February 2, 2011 doi:10.1152/jn.00537.2010.-The mechanical properties of the human arm are regulated to maintain stability across many tasks. The static mechanics of the arm can be characterized by estimates of endpoint stiffness, considered especially relevant for the maintenance of posture. At a fixed posture, endpoint stiffness can be regulated by changes in muscle activation, but which activation-dependent muscle properties contribute to this global measure of limb mechanics remains unclear. We evaluated the role of muscle properties in the regulation of endpoint stiffness by incorporating scalable models of muscle stiffness into a three-dimensional musculoskeletal model of the human arm. Two classes of muscle models were tested: one characterizing short-range stiffness and two estimating stiffness from the slope of the force-length curve. All models were compared with previously collected experimental data describing how endpoint stiffness varies with changes in voluntary force. Importantly, muscle properties were not fit to the experimental data but scaled only by the geometry of individual muscles in the model. We found that forcedependent variations in endpoint stiffness were accurately described by the short-range stiffness of active arm muscles. Over the wide range of evaluated arm postures and voluntary forces, the musculoskeletal model incorporating short-range stiffness accounted for 98 Ϯ 2, 91 Ϯ 4, and 82 Ϯ 12% of the variance in stiffness orientation, shape, and area, respectively, across all simulated subjects. In contrast, estimates based on muscle force-length curves were less accurate in all measures, especially stiffness area. These results suggest that muscle short-range stiffness is a major contributor to endpoint stiffness of the human arm. Furthermore, the developed model provides an important tool for assessing how the nervous system may regulate endpoint stiffness via changes in muscle activation. musculoskeletal model WE COMMONLY USE OUR HANDS to move and manipulate objects in different environments. Many of these tasks tend to destabilize arm posture (Rancourt and Hogan 2001). Nevertheless, they can be completed because the central nervous system regulates the mechanical properties of the arm to compensate for these instabilities, usually ensuring that the coupled system of the arm and its environment remains stable so that posture can be maintained (McIntyre et al. 1996). Understanding how this regulation occurs and the relative contributions of the nervous system and the intrinsic biomechanics of the arm remains an important problem in motor control.