Rationale: Secreted PLA₂s (sPLA₂)s play key regulatory roles in the biosynthesis of eicosanoids such as the cysteinyl leukotrienes (CysLT)s, but the role of these enzymes in the pathogenesis of asthma is not known. Objectives: To establish if sPLA₂s are overexpressed in the airways of asthmatics, and determine if these enzymes may play a role in the generation of eicosanoids in exercise-induced bronchoconstriction (EIB). Methods: Induced sputum samples were obtained from asthmatic subjects with EIB, and non-asthmatic controls at baseline, and on a separate day 30 min after exercise challenge. The expression of the PLA₂s in induced sputum cells and supernatant was determined by quantitative PCR, immunocytochemistry, and Western blot. Main Results: The sPLA₂s expressed at the highest levels in airway cells of asthmatics were groups X and XIIA. Group X sPLA₂ (sPLA₂-X) was differentially overexpressed in asthma and localized to airway epithelial cells and bronchial macrophages. The gene expression, immunostaining in airway epithelial cells and bronchial macrophages, and the level of the extracellular sPLA₂-X protein in the airways increased in response to exercise challenge in the asthma group, while the levels were lower and unchanged following challenge in non-asthmatic controls. Conclusions: Increased expression of sPLA₂-X may play a key role in the dysregulated eicosanoid synthesis in asthma.