Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (mø) to release tumor necrosis factor α (TNF-α). The IC50 of IL-10 for the suppression of TNF-α release induced by 0.5 μ g/ml lipopolysaccharide was 0.04 ± 0.03 U/ml, with as little as 1 U/ml suppressing TNF-ot production by a factor of 21.4 + 2.5. At 10 U/ml, IL-10 markedly suppressed mø release of reactive oxygen intermediates (ROI) (IC50 3.7 ± 1.8 U/ml), but only weakly inhibited mø release of reactive nitrogen intermediates (RNI). Since TNF-α is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that mOb exposed to low concentrations of IL-10 suppress lymphocytes, mø deactivated by higher concentrations of IL.10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-α, ROI, and RNI are major antimicrobial and tumoricidal products of mø. IL-10’s effects on mø overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse mø, transforming growth factor β and macrophage deactivation factor. Based on results with neutralizing antibodies, all three mø suppressor factors appear to act independently.