RANTES is a chemokine produced in delayed-type hypersensitivity (DTH) and allergic reactions, in which it may contribute to the recruitment of immune cells. Macrophages participate in the cellular infiltration in both conditions and they represent a potent source of RANTES. To understand the regulation of RANTES production by human monocytes, we analyzed the effect of cytokines and of corticosteroids on this production. We showed that IFN-gamma and tumor necrosis factor (TNF)-alpha cooperated to induce RANTES production by monocytes. N-acetylcysteine inhibited this effect, indicating that reactive oxygen intermediates are required for RANTES production. Both IL-10 and corticosteroids antagonized the stimulating effect of IFN-gamma and TNF-alpha on RANTES production. In contrast, IL-4 had no effect on IFN-gamma-induced RANTES production and it potentiated the positive effect of TNF-alpha on this production. Thus, the deactivating properties of IL-10 and corticosteroids on macrophage functions include RANTES production, and this may contribute to the immunosuppressive effect of both compounds in DTH and allergic reactions. In contrast, IL-4 has an opposite effect on RANTES production and this property may contribute to cell recruitment in allergic reactions. Therefore, although IL-10 and IL-4 belong to the Th2 family of cytokines, they can display distinct functions in immune reactions.