Virtual reality aims at reproducing reality and simulating actions like object manipulation tasks. Despite abundant past research on designing 3D interaction devices and methods to achieve close-to-real manipulation in virtual environments, strong differences exist between real and virtual object manipulation. Past work that compared between real and virtual manipulation mainly focused on user performance only. In this paper, we propose using also physiological signals, namely electromyography (EMG), to better characterize these differences. A first experiment featuring a simple pick-and-place task on a real setup and in a CAVE system showed that participants’ muscular activity reveals a clearly different spectrum in the virtual environment compared to that in reality.