We investigated the effect of 17beta-estradiol on mice resistant to infection by Trypanosoma cruzi. Infected Balb/C, C3H and C57BL/6 female mice had a longer survival time than males, C57BL/6 showing the highest difference (50% cumulative mortality in females versus 100% in males). This lineage was treated with estradiol (from 0.05 microg to 500 microg/mouse) 1 day before infection. Treatment with 50 microg or 500 microg estradiol/ mouse increased mortality and parasitaemia. Low doses had no effect or tended to reduce both parameters. Given that estradiol presented no in vitro effect on trypomastigotes or epimastigotes, the involvement of a direct hormonal effect on the parasite is improbable. Alterations in the humoral T. cruzi-specific response were also discarded, since the kinetics and concentration of anti-T. cruzi IgG were not affected by the treatment. Females infected during an estradiol-descending phase (meta-oestrus) survived longer than those infected during other phases of the oestrous cycle. We confirmed that estradiol interferes with T. cruzi infection.