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A framework to study the response of seated operators to whole-body vibration (WBV) is presented in this work. The framework consists of (i) a six-degree-of-freedom man-rated motion platform to play back ride files of typical heavy off-road machines; (ii) an optical motion capture system to collect 3D motion data of the operators and the surrounding environment (seat and platform); (iii) a computer skeletal model to embody the tested subjects in terms of their body dimensions, joint centers, and inertia properties; (iv) a marker placement protocol for seated positions that facilitates the process of collecting data of the lower thoracic and the lumbar regions of the spine regardless of the existence of the seatback; and (v) a computer human model to solve the inverse kinematics/dynamic problem for the joint profiles and joint torques. The proposed framework uses experimental data to answer critical questions regarding human response to WBV.