<lm> The isotype distribution of the antibody response against one Trypanosoma cruzi antigenic fraction, FIV, and the putative association to heart disease were analyzed in patients of two apparently genetically distinct Amerindian populations, Mataco (M) and Toba (T), infected with this parasite. The isotypes profiles were analyzed by ELISA, and the antigen specificity of IgG immune response was determined by the immunoblot method. The percentages of infected individuals with abnormal electrocardiograms (GII) were 50% for population M and 10% for population T. Many individuals from both populations had measureable IgG2, IgG3 and IgG4 antibodies to FIV, but the level and frequency (%) of positive sera in population T was considerably higher than in population M (70% vs 15% for IgG2; 75% vs 40% for IgG3; 85% vs 20% for IgG4). The level and frequency of IgG1 reactivity against FIV were similar in the two populations. When the sera were titrated, the most remarkable difference in isotype levels between populations T and M was seen for IgG2 and IgG4, the T population showing the highest titer. No association between clinical state and a particular isotype profile was found by ELISA in any population. When the antigen specificity of antibody response was determined by immunoblot, the antigen patterns recognized by sera from the two clinical groups showed some differences only in population M. All sera assayed from GII of population M fixed more IgG than those with normal electrocardiograms (GI). Two bands of 36 and 43 kD were revealed only in GII of this population. Similar antigenic patterns between the two clinical groups from population T were observed, and they were comparable with those obtained with GI from population M.