“Bronchial thermoplasty” — the direct application of thermal energy to the airway wall in the clinical setting — leads to reduction of the smooth muscle mass within the airway wall, reduced potential for bronchoconstriction and improvement in asthma symptoms. However the mechanism underlying this response has not yet been elucidated. We found a steep thermal sensitivity of isometric contractions in bovine airway smooth muscle: ∼0%, ∼50% and ∼100% reduction at 55°C, respectively. These changes in contractility developed within minutes after thermal treatment. This thermal sensitivity was shifted to lower temperatures by the TRPV2 agonist 2-APB (2-aminoethoxydiphenyl borate, 10-4 M). Likewise, the TRPV2 agonists 2-APB and tetrahydrocannabinol (10-4 M) evoked a large membrane conductance with linear current-voltage relationship and reversal potential of ∼0 mV. Immunohistochemistry showed TRPV2 to be distributed around the smooth muscle. These observations are all consistent with the involvement of TRPV2 in the thermal response of airway smooth muscle. Oddly, however, temperature-induced ablation of contractions was not prevented by agents which block conductance through TRPV2 channels (ruthenium red; La3+, Gd3+, capsaicin, removal of external Ca2+). We conclude that bronchial thermoplasty activates TRPV2 channels in the muscle, and that this in some way transduces into a disappearance of the smooth muscle cell (and thus loss of contractility). Furthermore, the data suggest these changes are not dependent upon the ionic currents per se through those channels; instead, they may involve a direct interaction between the channels and some intracellular entity(s).