Resistance to Trypanosoma brucei brucei has been correlated with the ability of infected animals to produce interferon (IFN)–γ and tumor necrosis factor (TNF) in an early phase of infection, followed by interleukin (IL)–4 and IL-10 in late and chronic stages of the disease. Contributions of IFN-γ and IL-10 in the control of parasitemia and survival of mice infected with T. brucei brucei were investigated by using IFN-γ^−/− and IL-10^−/− mice. Results suggest that IFN-γ, mainly secreted by CD8⁺ T cells, is essential for parasite control via macrophage activation, which results in TNF and nitric oxide secretions. IL-10, partially secreted by CD4⁺ T cells, seems to be important for the survival of infected mice. Its absence resulted in the sustained secretion of inflammatory mediators, which indicated the role of IL-10 in maintaining the balance between pathogenic and protective immune responses during African trypanosomosis