Interleukin (IL)-4, IL-10, and IL-13, Th2 cell–derived cytokines, play major roles in the pathophysiology of allergic diseases. These cytokines up-regulate or down-regulate the production of arachidonic acid metabolites. In this study, we have investigated the effect of IL-4, IL-10, IL-13, and other cytokines on A23187-stimulated synthesis of leukotriene (LT) B₄ in human polymorphonuclear leukocytes (PMNs). Production of LTB₄ was measured by specific radioimmunoassay and high performance liquid chromatography. Messenger RNA (mRNA) expression of cytosolic phospholipase A₂ (cPLA₂), 5-lipoxygenase (5-LO), and LTA₄ hydrolase, which were involved in the synthesis of LTB₄, was determined by reverse transcription–polymerase chain reaction and Northern blot analysis. Protein synthesis of their enzymes was determined by Western blot analysis. IL-4 and IL-13 enhanced A23187-stimulated LTB₄ synthesis and increased mRNA expression and protein synthesis of LTA₄hydrolase, but not those of cPLA₂ or 5-LO. These results indicate that IL-4 and IL-13 transcriptionally or post-transcriptionally up-regulate the synthesis of LTB₄, a potent chemotactic factor to PMNs, at the enzyme level of LTA₄ hydrolase, and this up-regulation mechanism may participate in the development of allergic inflammation.