Airway hyperresponsiveness (AHR) occurs in both asthma and COPD. In older people with asthma, AHR is associated with increased acinar ventilation heterogeneity, but it is unknown if this association exists in COPD.Thirty one COPD and 19 age-matched asthmatic subjects had measures of spirometry, lung volumes, exhaled nitric oxide, ventilation heterogeneity, and methacholine challenge. Indices of acinar (Sacin) and conducting (Scond) airway ventilation heterogeneity were calculated from the multiple breath nitrogen washout. Predictors of AHR were then determined.In COPD, AHR was predicted by lower Sacin and lower FVC (model r 2 =0.35, p=0.001). In asthma, AHR was predicted by higher Sacin and higher residual volume (model r 2 =0.62, p < 0.001).These findings suggest that airway responsiveness in COPD and asthma is determined by underlying disease-specific processes, rather than a common pattern of physiological abnormality. © 2013 Elsevier Ltd.V.