Successful vaccination of mice against an otherwise lethal challenge with the Peru strain of Trypanosoma cruzi necessitates the induction of a strong cell mediated immune response. Previously, immunization of mice with the paraflagellar rod proteins from Trypanosoma cruzi administered subcutaneously with Freund's adjuvant has been shown to elicit an Ag-specific cellular immune response that reduces parasitemia and provides 100% survival against an otherwise lethal challenge with the parasite. Since this vaccine regimen is unacceptable for use in humans, we have tested immunization regimens using PFR Ag in combination with alum and either recombinant murine IL-12 or a replication deficient adenovirus vector expressing murine IL-12. Here, it is shown that immunization of C57BL/6 mice with PFR Ag coadsorbed to alum with either recombinant IL-12 or adenovirus-expressing IL-12 induces a strong cellular immune response that results in 100% survival and >90% reduction in parasitemia in immunized mice challenged with the bloodstream stage of Trypanosoma cruzi.