In man, differential diagnosis of Trypanosoma cruzi and Trypanosoma rangeli infections represents a serious problem, not only because both parasites present similar geographical distribution, the same hosts and sometimes the same insect vector, but also because they have common antigen determinants. In this work IgM and IgG humoral responses to T. cruzi syntethic peptides in mice infected with T. cruzi and with T. rangeli were analysed. In a immunoradiometric assay (IRMA ) 6 syntethic peptides were used, denominated as clones 1, 2, SAPA, 13, 30 and 36. The results showed that sera from infected mice with T. rangeli recognized all peptides derived from T. cruzi proteins, at IgM as well as IgG level. Reactivity with peptide SAPA is discussed as previous work indicated that SAPA is not codified in the T. rangeli genome. Our results support the suggestion that crossed reactions are due to the fact that both parasites present common antigens. © 2007 Sociedad Chilena de Parasitología. Organo Oficial de la Federación Latinoamericana de Parasitólogos.