We investigated the effects of the Th₂-like cytokines IL-4 and IL-13 and of IL-10 on the induction of iNOS and NO production in rat eosinophils. Addition of mIL-4 to the eosinophil culture increased iNOS activity and nitrite production but did not improve the stimulatory effect of IFN-γ and LPS. In contrast to eosinophils, addition of mIL-4 to macrophage cultures inhibited the iNOS expression and nitrite production induced by IFN-γ plus LPS. Addition of mIL-13 to the eosinophil cultures did not significantly change iNOS activity and nitrite production in cells stimulated or not with IFN-γ plus LPS. On the other hand, IL-13 inhibited iNOS activity in IFN-γ plus LPS-stimulated macrophages. In the presence of IL-10, iNOS activity in non-stimulated eosinophil or macrophage cultures was not significantly altered, but the enzyme expression was inhibited in IFN-γ plus LPS-stimulated eosinophils or macrophages. The production of nitrite by eosinophils stimulated by IFN-γ plus LPS was inhibited by the presence of IL-10 in the medium. In conclusion, eosinophils might exhibit differential modulation of the l-arginine/iNOS pathway depending on the profile of Th₂ cytokines produced during allergic diseases. IL-4 appears to be an important Th₂ cytokine involved in the induction of the l-arginine/iNOS pathway in eosinophils.