We measured lung impedance (ZL) before and after four doses of methacholine (Mch) infusion in five intact chest (with esophageal balloon) and six open-chest dogs from 0.2 to 8 Hz with an optimal ventilator waveform. From ZL, we estimated airway resistance (R(aw)) and inertance (Iaw) and tissue viscance (GL) and elastance (HL). Two-way analysis of variance revealed that: (1) Mch had a strong influence on all parameters (p < 0.001), but small effect on hysteresivity, nL = GL/HL; (2) closed-chest GL and HL were significantly higher and Iaw lower than their open-chest values (p < 0.002, p < 0.05 and p < 0.0001); and (3) at the highest Mch dose, the relative increase in R(aw) was six times higher in the closed-chest condition. The reduced impact of Mch on open-chest mechanics may be due to constrictions superimposed on grossly different lung configurations and/or some humoral effects initiated by the thoracotomy. We conclude that Mch doses that elicit mild constriction in open-chest condition can cause a severe constriction in intact animals.