BALB/c male mice acutely infected with Trypanosoma cruzi underwent a severe weight loss (around 20%, from day 18 to 31 post-infection), when compared to age-matched uninfected animals. Though mice regained weight later, when blood parasites were hardly detectable, wasting extended over the chronic phase of infection. The onset and the magnitude of weight loss were related to the mouse susceptibility to infection, since they were respectively earlier and higher in male mice which will die than in surviving ones, in males than in females, and in BALB/c than in B6D2 [(C57B1/6 x DBA/2)F1], a mouse strain more resistant to infection. Fat weight of infected mice (male BALB/c) was reduced by 60 to 80%, whereas lean mass was unaffected and water content rose by 6 to 10% in acute and chronic infection. Haematocrit was also decreased by 15-16% in acute infection. Animals failed to compensate their energetic loss since their food intake remained similar to that of uninfected animals. Injections of neutralizing anti-TNF-alpha monoclonal antibody into infected male mice, during the first two weeks but not later in infection, significantly attenuated the weight loss. Early administration of anti-IL-6 or anti-IFN-gamma MoAbs did not improve the mouse wasting. Taken together, these data show that TNF is a key agent of cachexia occurring in the acute T. cruzi infection in mice.