Infection with Trypanosomacruzi, the agent of Chagas’ disease, results in elevated levels of interleukin-6 (IL-6) in serum and infected tissues. However, it remains unknown whether IL-6 plays a role in host defence against T.cruzi. To determine whether IL-6 underlies disease progression, we followed the time course of T.cruzi-infected mice bearing IL-6 +/+ and −/− genotypes, respectively. We found that IL-6 −/− mice were more susceptible to T.cruzi infection as they exhibited about 3-fold higher parasitaemia and died earlier than wild-type animals. Unlike what might be expected, T.cruzi-infected IL-6 −/− mice did not show at peak infection a decrease in the secretion of IFN-γ, a Th1 cytokine crucial for controlling the parasite. Instead, they exhibited a much reduced splenocyte recall response to T.cruzi antigens. Our results suggest that IL-6 mediates anti-parasite protective responses against T.cruzi.