Airway hyperresponsiveness (AHR) is commonly assessed by a methacholine challenge test (MCT), during which a provocative concentration causing a 20% reduction in forced expiratory volume in 1 second (FEV1 ) (PC20 ) < 8mg/ml is considered a positive response. However, a fall in specific airway conductance (sGaw) may also have clinical significance. The purpose of this study was to assess whether AHR determined by a provocative concentration causing a 40% reduction in sGaw (PC40 ) < 8mg/ml corresponds to a clinical diagnosis of asthma. We analysed the changes in spirometry, lung volumes and sGaw during MCT in 211 randomly selected patients being evaluated for AHR to support a clinical diagnosis of asthma. The mean (SD) age of the group was 53 (15) years, with 141 women (67%). Overall lung function was normal, with FEV1 =92 (15) % predicted, total lung capacity= 97 (13) % predicted and sGaw=0.19 (0.15-0.23) L/s/cm H2 O/L, (median, 25-75 IQR). There were many more patients who responded by PC40 only (n=120) than who responded by PC20 (n=52). There was no significant difference in asthma diagnosis between the PC20 (98%) and PC40 (93%) groups, and we estimate 34% of patients with a diagnosis of asthma would have been classified as having no AHR if only the FEV1 criterion was used. Changes in sGaw during MCT indicate clinically significant AHR in support of a clinical diagnosis of asthma among patients being evaluated for asthma.