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To investigate whether increased airway closure is a component of airway hyperresponsiveness (AHR), airway closure was compared during induced bronchoconstriction in 62 asthmatic, 41 non-asthmatic non-obese (control) and 20 non-asthmatic obese (obese) subjects. Airway closure and airway narrowing were measured by spirometry as the %∆FVC and ∆(FEV1/FVC), or forced expiratory ratio (∆FER). Multiple regression analyses were used to assess the determinants of AHR, assessed by the dose response slope (DRS). DRS was increased in asthmatics compared to controls (P < 0.001), but did not differ between obese and controls. The spirometric predictors of logDRS were baseline FER, ∆FER, BMI and %∆FVC (R2adj = 0.36, p < 0.0001). There was a negative relationship between BMI and logDRS in the regression, suggesting a protective effect. These findings suggest that the extent of airway closure during induced bronchoconstriction is a determinant of AHR, independent of the level of airway narrowing. However, after adjusting for airway closure, obesity appears to protect against AHR