T. cruzi shares antigenic determinants with preparations of the Ca sequestering ATPase of sarcoplasmic reticulum. The cross-reacting (SRA) is also apparently present on the sarcolemma of cardiac myofibers. Using highly specific reference antisera to either the small membranes of T. cruzi or to a tryptic fragment of striated muscle SRA, SRA is present in the striated muscle of animals representative of the evolutionary scale ranging from nonhuman primate to fish. The small membranes of 9 different T. cruzi strains isolated from widely divergent areas of the American continents also reacted with the reference antisera. SRA is present in these T. cruzi strains and may be prevalent among all T. cruzi strains. The shared T. cruzi-striated muscle antigen, SRA, may be a heteroantigen present in all T. cruzi strains and in the striated muscle of all classes of animals. Immunization of rabbits (3 of 5) or chickens (5 pairs of 5 pairs) with striated muscle membrane preparations of different classes of animals, particularly those of a nonhuman primate, chicken and turtle, gave rise to IgG anti-allogeneic striated muscle antibody activity. Immunization of rabbits (4 of 9) and chickens (5 pairs of 6 pairs) with the small membranes of different T. cruzi strains also produced IgG anti- allogeneic striated muscle. T. cruzi shares cross-immunogenicity with striated muscle SRA. Since SRA is apparently present on the sarcolemma of cardiac myofibers, it may be implicated in the immunopathogenesis of Chagas'' disease.