Secretory phospholipases A(2) (sPLA(2)s) are molecules released in plasma and biologic fluids of patients with systemic inflammatory, autoimmune, and allergic diseases. Several sPLA(2) isoforms are expressed and released by such human inflammatory cells as neutrophils, eosinophils, basophils, T cells, monocytes, macrophages, and mast cells. Certain sPLA(2)s release arachidonic acid, thereby providing the substrate for the biosynthesis of proinflammatory eicosanoids. However, there are other mechanisms by which sPLA(2)s might participate in the synthesis of lipid mediators. Interestingly, sPLA(2)s activate inflammatory cells through mechanisms unrelated to their enzymatic activity. Several sPLA(2)s induce degranulation of mast cells and eosinophils and activate exocytosis in macrophages. Furthermore, sPLA(2)s promote cytokine and chemokine production from macrophages, neutrophils, eosinophils, monocytes, and endothelial cells. Some of these effects are mediated by the binding of sPLA(2)s to specific receptors expressed on effector cells. Thus sPLA(2)s might play important roles in the initiation and amplification of the inflammatory reaction. Selective inhibitors of sPLA(2)s and specific antagonists of sPLA(2) receptors might prove useful in the treatment of allergic and autoimmune diseases, such as bronchial asthma and rheumatoid arthritis.