AbstractSchwann cells within a peripheral nerve respond robustly after an axonal injury. Recent results have revealed that Schwann cells undergo concurrent proliferation and apoptosis after a chronic nerve injury that is independent of axonal pathology. Although the exact nature of the stimulus that produces this Schwann cell response remains unknown, we postulated that this response may be triggered directly by mechanical stimuli. Thus, we sought to determine how pure Schwann cells responded to a sustained shear stress in the form of laminar fluid flow by evaluating for proliferation, expression of S‐100, myelin‐associated glycoprotein (MAG), and myelin basic protein (MBP). Immunohistochemistry demonstrated that the Schwann cells were positive for S‐100, MAG, and MBP in greater than 99% of the experimental cells. Stimulated cells also revealed an increased rate of proliferation by as much as 100% (p <.001). The mRNA expression of MAG and MBP was down‐regulated by 21% (p <.035) and 18% (p <.015), respectively, in experimental cells from RT‐PCR assays. Furthermore, Western blot showed a down‐regulation in MAG and MBP protein expression by 29% (p <.035) and 35% (p <.02), respectively. This study provides novel information regarding Schwann cell direct response to this physical stimulus that is not secondary to an axonal injury. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.