During the late phase (LP) response to inhaled allergen, mediators from neutrophils and eosinophils are released within the airways, resembling what occurs during an asthma attack. We compared the distribution of obstruction and degree of reversibility that follows a deep inspiration (DI) during early phase (EP) and LP responses in 9 asthmatics challenged with allergen. Heterogeneity of constriction was assayed by determining frequency dependence of dynamic lung resistance and elastance, airway caliber by tracking airway resistance during a deep inspiration, and airway inflammation by measuring inflammatory cells in induced sputum post-challenge. Despite a paucity of eosinophils in the sputum at baseline (less than 1% of non-squamous cells), asthmatics showed a substantial EP response with highly heterogeneous constriction and reduced capacity to maximally dilate airways. The LP was associated with substantial airway inflammation in all subjects. However, five subjects showed only mild late phase constriction (LP-) while four showed more marked LP constriction (LP+) characterized by heterogeneous constriction similar to EP. Bronchoconstriction during LP was fully alleviated by administering a bronchodilator. These findings, together with the impaired bronchodilatory response during a DI, indicate a physiologic abnormality in asthma at the smooth muscle level and that airway inflammation in asthma is associated with a highly non-uniform pattern of constriction. These data support the hypothesis that variability in responsiveness among asthmatics derives from intrinsic differences in smooth muscle response to inflammation.