The aim of this work was to study whether Trypanosoma cruzi infection could elicit humoral immune response to the well-defined parasite antigen acidic fraction separated from T. cruzi cytosol by isoelectric focusing and designated fraction IV (FIV) and whehter this response could account for some of the autoreactive immune response against peripheral nerve components. Chagasic patients with positive serology for Chagas' disease were classified as group I (n = 12) with normal electrocardiograms (ECG) and no signs of disease, group II (n = 12) with EGG abnormalities but without cardiomegaly, and group III (n = 12) with cardiomegaly and congestive heart failure. Sera from patients in group II showed the highest frequency of positive reactivity against FIV. Ninety-two percent had titers higher than 1/400 while the percentage for groups I and III was 50%. The autoreactive response against human sciatic nerve saline etract (SNS) was studied. The binding of IgG to SNS was positive in groups I (58%), II (66%), and III (75%) patients. The treatment of SNS with periodate diminished the ability of antigens to fix IgG from these chagasic patients. Absorption studies were performed to investigate whether FIV and SNS could have cross-reactive epitopes. Preabsorption of positive sera with FIV inhibited 48–69% of samples' reactivity against antigen. In contrast, preabsorption of positive sera with SNS inhibited only 12–23% of samples' reactivity against antigen. Overall, these results suggest that FIV-T. cruzi and sciatic nerve components possess some epitopes, possibly of a carbohydrate nature, in common. Thus, infection in Chagas' disease could overcome the tolerance to self components and could lead to autoimmunity.