We hypothesized that there are clinically relevant differences in eosinophil integrin expression and activation in patients with asthma. To evaluate this, surface densities and activation states of integrins on eosinophils in blood and bronchoalveolar lavage (BAL) of 19 asthmatic subjects were studied before and 48 h after segmental Ag challenge. At 48 h, there was increased expression of α D and the N29 epitope of activated β 1 integrins on blood eosinophils and of α M, β 2, and the mAb24 epitope of activated β 2 integrins on airway eosinophils. Changes correlated with the late-phase fall in forced expiratory volume in 1 s (FEV 1) after whole-lung inhalation of the Ag that was subsequently used in segmental challenge and were greater in subjects defined as dual responders. Increased surface densities of α M and β 2 and activation of β 2 on airway eosinophils correlated with the concentration of IL-5 in BAL fluid. Activation of β 1 and β 2 on airway eosinophils correlated with eosinophil percentage in BAL. Thus, eosinophils respond to an allergic stimulus by activation of integrins in a sequence that likely promotes eosinophilic inflammation of the airway. Before challenge, β 1 and β 2 integrins of circulating eosinophils are in low-activation conformations and α D β 2 surface expression is low. After Ag challenge, circulating eosinophils adopt a phenotype with activated β 1 integrins and up-regulated α D β 2, changes that are predicted to facilitate eosinophil arrest on VCAM-1 in bronchial vessels. Finally, eosinophils present in IL-5-rich airway fluid have a hyperadhesive phenotype associated with increased surface expression of α M β 2 and activation of β 2 integrins.