Polyclonal antisera were obtained in rabbits following immunization with disrupted epimastigote or trypomastigote forms; 8-methoxypsoralen-inactivated trypomastigotes; and surface trypomastigote antigens shed into the medium. High antibody levels were induced by all preparations as observed by indirect immunofluorescence and ELISA. However, antibodies promoting complement-mediated lysis of bloodstream forms were only detected in animals immunized with inactivated living trypomastigotes and shed surface antigens. Immunoprecipitation of radioiodinated parasites showed that sera with lytic antibodies bound strongly to a wide range of membrane polypeptides from 72 to 160 kDa. Immunoadsorption of antibodies from a serum with high lytic activity on specific classes of trypomastigote polypeptides indicated that independent antigens are targets of lytic antibodies and that common epitopes may exist in different trypomastigote components.