The mouse is the most extensively studied animal species in respiratory research, yet the technologies available to assess airway function in conscious mice are not universally accepted. We hypothesized that whole body plethysmography employing non-invasive restraint (RWBP) could be used to quantify specific airway resistance (sRaw-RWBP) and airway responsiveness in conscious mice. Methacholine (Mch) responses were compared using sRaw-RWBP versus airway resistance by the forced oscillation technique (Raw-FOT) in groups of C57, A/J, and BALBc mice. SRaw-RWBP was also compared to sRaw derived from double chamber plethysmography (sRaw-DCP) in BALBc. Finally, airway responsiveness following allergen challenge in BALBc was measured using RWBP. SRaw-RWBP in C57, A/J, and BALBc mice was 0.51±0.03, 0.68±0.03, and 0.63±0.05 cm*sec, respectively. sRaw derived from Raw-FOT and FRC (Raw*FRC) was 0.095cm*sec, approximately 1/5^th of sRaw-RWBP in C57 mice. The intra- and inter-animal coefficients of variations were similar between sRaw-RWBP (6.8 and 20.1%) and Raw-FOT (3.4 and 20.1%, respectively). The order of airway responsiveness employing sRaw-RWBP was AJ>BALBc>C57 and for Raw-FOT was AJ>BALBc=C57. There was no difference between the airway responsiveness assessed by RWBP vs. DCP; however baseline sRaw-RWBP was significantly lower than sRaw-DCP. Allergen challenge caused a progressive decrease in ED175 based on sRaw-RWBP. In conclusion, the technique of RWBP was rapid, reproducible, and easy to perform. Airway responsiveness measured using RWBP, DCP, and FOT was equivalent. Allergen responses could be followed longitudinally which may provide greater insight into the pathogenesis of chronic airway disease.