An experimental Trypanosoma cruzi 90 kDa cell surface glycoprotein (GP90) vaccine, previously shown to be protective in mice is similarly effective in marmosets (Callithrix jacchus jacchus). Protection in the mouse is completely dependent on the adjuvant saponin and immunological studies confirm that GP90 is intrisically poorly immunogenic. Both specific antibody and cell mediated immunity are potentiated strongly by saponin and the resulting protective immunity is long lasting (six months). It is effective against the naturally infective, insect-metacyclic, form and a range of heterologous T. cruzi strains including a low mouse passage human isolate. Sterile immunity (that is, complete elimination of parasites) was not, however, achieved. Evidence is presented that the levels of tissue damage associated with acute infection, as measured by production of auto anti-tissue immunoglobulins, are significantly reduced in GP90-immunized mice. These and other results are discussed in terms of the desired characteristics for vaccine use of T. cruzi antigens.