GM-CSF plays an important role in inflammation by promoting the production, activation, and survival of granulocytes and macrophages. In this study, GM-CSF knockout (GM-CSF-/-) mice were used to investigate the role of GM-CSF in a model of allergic airway inflammation. In allergic GM-CSF-/- mice, eosinophil recruitment to the airways showed a striking pattern, with eosinophils present in perivascular areas, but almost completely absent in peribronchial areas, whereas in wild-type mice, eosinophil infiltration appeared in both areas. In the GM-CSF-/- mice, mucus production in the airways was also reduced, and eosinophil numbers were markedly reduced in the bronchoalveolar lavage (BAL)3 fluid. IL-5 production was reduced in the lung tissue and BAL fluid of GM-CSF-/- mice, but IL-4 and IL-13 production, airway hyperresponsiveness, and serum IgE levels were not affected. The presence of eosinophils in perivascular but not peribronchial regions was suggestive of a cell migration defect in the airways of GM-CSF-/- mice. The CCR3 agonists CCL5 (RANTES) and CCL11 (eotaxin-1) were expressed at similar levels in GM-CSF-/- and wild-type mice. However, IFN-? mRNA and protein were increased in the lung tissue and BAL fluid in GM-CSF-/- mice, as were mRNA levels of the IFN-?-inducible chemokines CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-Tac). Interestingly, these IFN-?-inducible chemokines are natural antagonists of CCR3, suggesting that their overproduction in GM-CSF-/- mice contributes to the lack of airway eosinophils. These findings demonstrate distinctive abnormalities to a model of allergic asthma in the absence of GM-CSF.