The traditional whole body plethysmograph (WBP) relies on pressure changes induced by a freely respiring animal inside a chamber. This pressure is a combination of a thermo-hygrometric effect (proportional to tidal volume) and a gas compression effect (related to lung mechanics). In order to measure either tidal volume or lung mechanics, it must be assumed that the other component is negligible. In this research, an acoustic WBP was developed that is capable of measuring the thoracic volume change of a mouse independent of the thermohygrometric effect. This allows independent measurement of tidal volume and specific airway resistance.;In the first phase of this research, the plethysmograph was designed to optimize measurement of the acoustic signal, which involved minimizing the WBP pressure. This plethysmograph was designed as a resonating cavity at a fixed frequency. It had a sharp resonant peak and was tuned so that changes in body volume produced nearly linear changes in sound amplitude. The plethysmograph was tested with a water filled balloon connected to a syringe pump. The volume of the balloon was varied as a triangle wave with amplitude of 250 mu L. The RMS error between measured and delivered volume was 4.43 mu L. A volume step test, performed to assess the response time of the system, showed that the plethysmograph responded in less than one millisecond.;Next, the plethysmograph was redesigned to provide a compromise between the acoustic measurement and the WBP pressure measurement. Similar to traditional methods utilizing a double chamber plethysmograph, these measurements were combined to estimate specific airway resistance (sRaw). To evaluate the system, six conscious A/J mice were individually placed in a chamber for a two-minute exposure to aerosolized methacholine chloride dissolved in saline (0, 5, 10, and 20 mg/mL) which is known to increase sRaw in mice. Following exposure, the mice were transferred to the acoustic plethysmograph for data collection. The mean baseline value of sRaw was 0.93 +/- 0.10 cm H 2O · sec. A dose-dependent increase in sRaw was shown, with an approximate tripling of sRaw at the highest dose. These results are comparable to those of other methods reported in the literature.;key terms. specific airway resistance, Helmholtz resonator, unrestrained plethysmograph, whole-body plethysmograph, acoustic plethysmograph.