Recombinant mouse interleukin 10 (IL-10) was found to be highly effective in suppressing the release of tumor necrosis factor α (TNF-α) by mouse peritoneal macrophages (mφ). The IC50 for IL-10 to suppress TNF-α release induced by lipopolysaccharide (LPS) was 0.04 ± 0.03 U/ml, with as little as 1 U/ml suppressing TNF-α production by a factor of 21.4 ± 2.5. At higher concentrations (10 U/ml), IL-10 also significantly reduced the release of reactive oxygen intermediates (ROI) but had only a weak effect on the release of reactive nitrogen intermediates (RNI). Since TNF-α is a T cell growth and differentiation factor, while ROI and RNI inhibit lymphocyte function, mφ exposed to low concentrations of IL-10 may suppress lymphocytes. Higher concentrations of IL-10 might deactivating mφ, making them permissive for the growth of microbial pathogens and tumor cells, as TNF-α, ROI, and RNI are major antimicrobial and tumoricidal products of mφ. IL-10's effects on mφ are distinct from those of transforming growth factor β and macrophage deactivating factor (MDF), and all three suppressor factors appear to act independently.Recombinant mouse interleukin 10 (IL-10) was found to be highly effective in suppressing the release of tumor necrosis factor α (TNF-α) by mouse peritoneal macrophages (mφ). The IC50 for IL-10 to suppress TNF-α release induced by lipopolysaccharide (LPS) was 0.04 ± 0.03 U/ml, with as little as 1 U/ml suppressing TNF-α production by a factor of 21.4 ± 2.5. At higher concentrations (10 U/ml), IL-10 also significantly reduced the release of reactive oxygen intermediates (ROI) but had only a weak effect on the release of reactive nitrogen intermediates (RNI). Since TNF-α is a T cell growth and differentiation factor, while ROI and RNI inhibit lymphocyte function, mφ exposed to low concentrations of IL-10 may suppress lymphocytes. Higher concentrations of IL-10 might deactivating mφ, making them permissive for the growth of microbial pathogens and tumor cells, as TNF-α, ROI, and RNI are major antimicrobial and tumoricidal products of mφ. IL-10's effects on mφ are distinct from those of transforming growth factor β and macrophage deactivating factor (MDF), and all three suppressor factors appear to act independently.