Here, we show that antigal antibodies from Chagas' disease patients react with noninfected host cells previously treated with antigens secreted by the trypomastigote forms of Trypanosoma cruzi. With the exception of human and Old World monkey cells, which are GAL‐negative, cells of all mammals express the GAL epitope (Galα(1‐3)Galβ(1‐4)GIcNAc‐R) on their surface. Thus only the former ones develop antigal antibodies. Antigal antibodies increase during infection with T. cruzi, which expresses GAL epitopes on the surface of the infective forms. Here, we show that incubation of noninfected, GAL‐negative cells with antigens shed by T. cruzi renders these cells reactive to antigal antibodies purified from chagasic sera. Neither chagasic sera depleted of antigal antibodies nor antigal antibodies purified from normal sera display reactivity with treated cells. Cell reactivity of chagasic antigal was abolished in the presence of melibiose (Galα(1‐6)Glc) or gal‐gal (methyl 3‐O‐α‐D‐galactopyranosyl α‐D‐galactopyranoside). Since shedding of T. cruzi antigens can occur in vivo, these antigens may induce reactivity of chagasic antigal with noninfected human cells. The reactivity of noninfected, GAL‐negative cells observed only with chagasic antigal antibodies can amplify the range of reactivity of these antibodies and consequently adds to their importance in the pathogenesis of human Chagas' disease. J. Clin. Lab. Anal. 12:108–114, 1998. © 1998 Wiley‐Liss, Inc.