This paper deals with the enhancement of natural antibodies in mice immunized with a previously purified exoantigen of Trypanosoma cruzi from infected mouse plasma by isoelectric focusing, called Ea 4.5. A simultaneous rinse of IgG antibodies recognizing acidic sciatic nerve antigen (SNA) and other conserved antigens such as myoglobin, actin, thyroglobulin, and tubulin was observed. The highest level of antibodies was revealed when myoglobin was used as antigen in the ELISA test. Good correlation was found between the level of antibodies reactive with SNA and with highly conserved antigens. Furthermore, absorption experiments showed that a fraction of antibodies binding SNA are polyreactive and also react with the highly conserved antigens. The histological studies of sciatic nerve, heart and skeletal muscle performed 1 month after the last immunization revealed no modifications with respect to the control animals. Based on these and a previous result [1], indicating that injection of Ea 4.5 induced in mice a partial protection against T. cruzi, the possibility exists that a percentage of antibodies induced by Ea 4.5 may correspond to the natural autoantibody type and take part in protective and/or pathogenic effects.