Reactivity to Trypanosoma cruzi antigens and autoreactivity to heart antigens were evaluated in 27 patients with Chagasic cardiomyopathy (group I), 52 patients without evidence of cardiac dysfunction (group II), and 36 selected controls, either healthy patients or patients with other heart diseases (group III). The in vitro lymphoblastogenesis response to T. cruzi antigens was found to be high in groups I and II and low in group III. The mean stimulation index to T. cruzi antigens, in fact, tended to be highest in group I, suggesting a more intense immune response in patients with Chagasic cardiomyopathy. The proportion of individuals with reactivity to heart antigens was 28.6% in group I, 25% in group II, and 0% in group III. The finding of an equal percentage of reactivity to heart antigens in groups I and II was unexpected, as a higher incidence of positive reactions in group I was predicted. Consequently, it is thought that this finding and its relevance to the pathogenic process of Chagasic cardiomyopathy need to be carefully assessed in a longitudinal study.