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This paper presents a novel active body weight support (BWS) method, which is capable of virtually offloading full or partial body mass for a potential application of enhancing treadmill-based locomotion rehabilitation. The mass-offloading capability is realized by actively compensating a desired amount of body weight and inertia force using an acceleration-feedback scheme. The method has been studied by dynamics simulations and a specially designed nonhuman experiment. In the simulation study, the human and the BWS device were modeled as a multibody dynamical system interacting dynamically with the treadmill. The ground reaction forces were recorded as the dynamic load on the person. A cam-slider-based experiment was designed and conducted to test the engineering feasibility of the mass-offloading capability. Both the simulation and experiment results demonstrated that the BWS system can compensate any desired amount of gravity force and inertia force and, therefore, has the effect of virtually reducing the mass of a person attached to the system.