It is well established that in humans many differences between right- and left-handers, anatomical, physiological and functional, exist. Left- and mixed-handedness is associated with greater bihemispheric representation of cognitive functions than in right-handers. Several studies indicate a left-right asymmetry in the function of hearing pathways between cochlea and auditory cortex, and furthermore, that this asymmetry is associated with handedness. Our investigation focuses on the medial olivo-cochlear system, which has been demonstrated to be more effective in the right than left ear in right-handers. The aim of the study was to investigate this auditory efferent system asymmetry according to handedness, gender, eyedness, footedness and the presence of spontaneous otoacoustic emissions. The medial efferent system has been found to be more effective in the right than left ear in right-handers, while functioning symmetrically in left-handers. Furthermore, the olivo-cochlear system, assumed to be involved in basic language processing, shows an asymmetrical pattern of functioning influenced by handedness as well as by hemispheric language representation. Reverse medial efferent system asymmetry was observed in left-handers compared to that in right-handers, on condition that only left-handed males were considered, or that the left-handers were also left-eyed, or that spontaneous otoacoustic emissions were present in the left ear of the left-handers, or when only left-handers without mixed-handers were considered.