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Cellular immune responses to recombinant (r) Sm14 were examined in chronic, treated patients and uninfected individuals living in an endemic area for schistosomiasis. The lymphocyte proliferative responses and cytokine profile to this antigen were evaluated. Peripheral blood mononuclear cells (PBMC) of all groups studied proliferated to rSm14. However, the highest proliferation index to rSm14 was detected in uninfected endemic normal (EN) individuals who are naturally resistant to schistosomiasis. Regarding the cytokines produced, the levels of interleukin (IL)‐5 and IL‐10, known as Th2 cytokines, were not statistically different among all groups studied. In contrast, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α were produced in significantly higher amounts by PBMC of EN individuals following rSm14 stimulation. Additionally, we have determined by flow cytometry that CD4+ T cells from these individuals are the main lymphocyte subpopulation producing IFN‐γ and TNF‐α. Moreover, we have used rIL‐10 or rIFN‐γ, or monoclonal antibodies (MoAb) against these two cytokines to determine their role on cellular reactivity to rSm14. Exogenous IL‐10 suppressed T‐cell proliferation and neutralization of endogenous IL‐10 restored lymphocyte activation and enhanced IFN‐γ and TNF‐α production in chronically infected patients. In contrast, the addition of anti‐IFN‐γ totally abrogated the PBMC proliferation within the EN group. This study demonstrated that IL‐10 is an important cytokine down‐regulating T‐cell responses in chronic schistosomiasis, whereas lymphocyte proliferation in the uninfected resistant group is dependent on IFN‐γ. Taken together these results suggest that Th1 type of immune response induced in EN individuals to a specific schistosome antigen might be associated with resistance to infection and also highlighted the importance of Sm14 as a potential vaccine candidate.