A very large number of people in both Americas are infected with T. cruzi. Nevertheless, only a relatively small percentage of them present clinical and pathological symptoms ascribable to this infection. The different immune reactions in Chagas' disease (American Trypanosomiasis) are reviewed and discussed here, both in their protective capacity and in their probable role in the pathogenesis of Chagas' disease clinical manifestations. Antibody responses are always present in infected subjects, and several types of specific antibodies have been demonstrated; their titers are high, more so in the acute phase of the disease. Their protective capacity in vivo has been demonstrated by several groups. T cell mediated immune responses (CMIR) have also been demonstrated in patients and experimental animals, but their presence is inconsistent and their level is generally low. Nevertheless, thymus dependent immune reactions are important in anti-T. cruzi protection, as shown by experiments in T deficient animals and also by some observations in immunodepressed patients. Antibody-dependent cell mediated cytotoxicity (ADCC) and natural killer (NK) cell activity directed against T. cruzi have also been proven in vitro, but their role in vivo is still unknown. There is no doubt that the immune system is able to recognize T. cruzi antigens and to protect the host against massive infection, but the immune response is not able to eliminate all the parasites, so that chronic infection ensues: this failure in "curing" the infection may be due to the above mentioned low level of CMIR and/or to escape mechanisms evolved by the parasite. The presence of immune reactions directed against self antigens in Chagas' disease patients and in experimental models of chronic Chagas' disease is also reviewed. These reactions may be due either to self antigens released by injured cells (and would then only be an epiphenomenon), or to cross-reacting antigens common to T. cruzi and normal components of the host; in fact, several cross-reactions have been proven between T. cruzi and laminin, nerve tissue antigens, etc. This would point to the possibility that autoimmune reactions play an important role in the pathogenesis of Chagas' disease clinical symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)