Exoantigens (Ea) of Trypanosoma cruzi released in blood during the acute phase of experimental murine infection and recognized as antigens by sera from chagasic patients were grouped into two zones: one zone of pI 4-5 (Ea4-5), which had components of 35 kDa, 50 kDa and slightly higher than 100 kDa, MW, and another zone, of pI 6-7 (Ea 6-7), with Ea of 50 kDa, 66-80 kDa and higher than 100 kDa. Immunization of mice with Ea4-5 or Ea6-7 prior to infection induced a protective immune response, as judged by levels of parasitaemia which were significantly lower than those of controls. Analysis of the immune response by skin test revealed that both groups of Ea induced immediate type hypersensitivity, the values of which were higher in animals immunized with Ea4-5. These antigens also induced specific cellular immunity (delayed-type hypersensitivity). There was a direct correlation between intensity of reactivity and the drop in the number of blood forms of parasites in these animals. Antibodies able to fix the epimastigote surface were also detected by ELISA and the immunofluorescence test in mice immunized with Ea4-5 or Ea6-7. There were no qualitative or quantitative differences in the antibody induced by the two groups of Ea; the main isotypes of these antibodies which recognized Ea expressed on the parasite surface were IgG1 and IgG2.