We have previously shown that inoculation of Trypanosoma cruzi clone-CL-14 generates efficient protective immunity against virulent T. cruzi and no infection or histopathology per se, indicating that it induces an immune state different from that exhibited by infected animals. To understand the basis of this difference, we screened CL-14-vaccinated mice for T cell abnormalities thought to be involved in the genesis of pathology. Lymphocytes from vaccinated mice present normal proliferative responses to concanavalin A; enhanced responses to T. cruzi antigens; do not show evidence of polyclonal activation (increased blast transformation and lymphocyte numbers) or changes in the density of CD4, CD8 and TCR-beta expression. Also, vaccinated mice display transient expansion of CD8+ lymphocytes expressing activated phenotypes (CD11a(hi) CD45RBlo CD62Llo). In view of the absence of pathology in vaccinated animals, the absence of immunosuppression and the restoration of a resting immune state reinforce the benign nature of this immunization.