We retrospectively analyzed 198 methacholine inhalation challenges (MICs) of symptomatic patients with normal results of lung examinations, spirometry, and chest radiographs. During MIC, five parameters (FEV1, FEF25-75%, FVC, sGaw, TGV) were measured. Using established changes in these parameters at < or = 8 mg/ml methacholine, there were 175 positive tests (no false positives) and 23 negative tests (15 true negatives, 5 false negatives, and 3 unavailable for follow-up). The MIC sensitivity determined by FEV1 responses was significantly lower than the sensitivity using responses in either three (FEV1, FEF25-75%, and FVC; p < 0.001) or five (FEV1, FEF25-75%, FVC, sGaw, and TGV; p < 0.001) parameter sets. Sensitivities were 60.6 percent, 91.1 percent, and 97.2 percent, respectively. All positive MICs (100 percent) were identified by examining changes in the five-parameter set vs 97.3 percent in the three-parameter set; it was a significant difference at p < 0.01. We conclude that the measurement and analysis of non-FEV1 parameters in addition to FEV1 significantly increases the sensitivity of the MIC.