Reflex responses recorded from the upper and lower divisions of the human orbicularis oris muscle were studied as a function of the site of stimulation. Stimuli were applied to 11 sites, ranging from the glabrous skin of the upper and lower lip vermilion borders to the hairy skin of the cheek. Highly localized, innocuous mechanical stimuli were created by displacing a servo-controlled probe over the surface of the perioral skin. Reflex response amplitude was strongly dependent on the site of stimulation. Stimulation of some sites, for example the ipsilateral corner of the mouth, the chin, and cheek, produced no responses, whereas stimulation of other sites, particularly the ipsilateral vermilion borders, produced large reflex responses. Changes in response amplitude as a function of stimulation site were the same for the upper lip and lower lip muscle recordings, with the largest responses at both recording sites produced by stimulation of the ipsilateral upper lip vermilion border. These results suggest that the upper and lower divisions of orbicularis oris share common synaptic drive, at least from inputs generated via reflex pathways, and that the upper vermilion border may be more densely innervated with mechanoreceptors than the lower. The latter hypothesis was supported by an additional experiment examining two-point discrimination thresholds for the glabrous skin of the upper and lower lips. Two-point thresholds were significantly smaller for the upper compared with the lower lip vermilion border.