The pathogenesis of Chagas' disease has been subject of active research and still remains to be ascertained. Galectin-1 (Gal-1), a member of a conserved family of animal beta-galactoside-binding proteins, localized in human heart tissue, has been suggested to play key roles in immunological and inflammatory processes. In the present study we demonstrated the occurrence of anti-Gal-1 autoAb in sera from patients in the acute and chronic stages of Chagas' disease (ACD and CCD) by means of ELISA and Western blot analysis. We found a marked increase in the level and frequency of Ig E anti-Gal-1 antibodies in sera from patients with ACD, but a low frequency of Ig M anti-Gal-1 immunoreactivity. Moreover, Ig G immunoreactivity to this beta-galactoside-binding protein was found to be correlated with the severity of cardiac damage in CCD, but was absent in nonrelated cardiomyopathies. We could not detect immunoreactivity with Trypanosoma cruzi antigens using a polyclonal antibody raised to human Gal-1 and no hemagglutinating activity could be specifically eluted from a lactosyl-agarose matrix from parasite lysates. Moreover, despite sequence homology between Gal-1 and shed acute phase antigen (SAPA) of T. cruzi, anti-Gal-1 antibodies eluted from human sera failed to cross-react with SAPA. In an attempt to explore whether Gal-1 immunoreactivity was originated from endogenous human Gal-1, we finally investigated its expression levels in cardiac tissue (the main target of Chagas' disease). This protein was found to be markedly upregulated in cardiac tissue from patients with severe CCD, compared to cardiac tissue from normal individuals.