Rationale: Nitric oxide is released from vascular endothelium in response to increased pulsatile shear stress. Nitric oxide inhibits mast cell activation, is anti-inflammatory and so might be protective in asthma. Objectives: We determined if a non-invasive, motion platform that imparts periodic sinusoidal inertial forces to the whole body along the spinal axis (pGz) causing release of endothelial nitric oxide, modulates experimental asthma in sheep. Methods: Allergic sheep were either untreated (control), treated with pGz alone or after receiving intravenously, the nitric oxide synthase inhibitor, N_w -Nitro-L-arginine methyl ester (L-NAME), before aerosol challenge with Ascaris suum and the effect on antigen-induced airway responses determined. Bronchoalveolar lavage cells obtained 6 hours after antigen challenge were analyzed for nuclear factor-kappa beta activity in the respective groups. Results: One-hour pGz treatment prior to antigen challenge, reduced the early airway response and blocked the late airway response, but did not prevent the antigen-induced airway hyperresponsiveness 24 hours after challenge. Administration of L-NAME before pGz completely reversed this protection, whereas L-NAME alone did not affect the antigen-induced responses. Nuclear factor-kappa beta activity was 1.9- and 1.8- fold higher in the control and L-NAME+pGz groups, respectively, compared to pGz treated animals. Extending the pGz treatment to twice daily for 3 days and then 1 hour before antigen challenge blocked the early and late airway responses, the 24-hour airway hyperresponsiveness and airway inflammatory cell response. Conclusion: Whole body pGz modulates allergen-induced airway responses in allergic sheep