Abstract Rationale The cytokine IL-13 plays an important role in inducing features of asthma including airway hyperresponsiveness (AHR). We previously reported the effect of IL-13 and mIL-13Rα2 on AHR in vivo (ATS, 2003). The purpose for this study is to determine the effect of IL-13 and mIL-13Rα2 on ASM function in vitro. Methods Tracheas were isolated from Balb/c mice. Tracheas were incubated for 18 hours at 4°C with 1μg/ml IL-13, and others in IL-13 and 1mg/ml of the mIL-13Rα2. Tracheas were suspended in a muscle bath containing Krebs buffer, and gassed with 95% O 2 and 5% CO 2 throughout the duration of concentration response and maintained at pH=7.4. Responses to KCl were determined along with concentration response curve (CRC) to both acetylcholine (Ach) and isoproterenol (Iso). Results Following IL-13, no significant increase in response to Ach was observed (p=0.063), but relaxation response to Iso was significantly attenuated (p Conclusion IL-13 significantly inhibits the relaxation response to Iso in vitro. The mIL-13Rα2 significantly inhibits the ability of IL-13 to induce this effect. This IL-13 antagonist is a potential therapeutic modality in asthma.