We have followed CD4 and CD8 TCR V beta repertoires during the acute phase of Trypanosoma cruzi infection in a resistant mouse strain (C57BL/6). No major changes were found in the V beta TCR distributions analyzed (covering roughly 40% of the TCR repertoire) in peripheral CD4 T lymphocytes, confirming the polyclonal nature of CD4 T cell responses. In contrast, in most animals, an over-representation of V beta 5 and V beta 14 TCR families was disclosed in the CD8 T cell compartment, superimposed on a predominantly polyclonal response. The preferential expansion of V beta 5+CD8+ T cells was also observed after infection of sensitive (C3H/HeJ, BALB/c) mouse strains. These observations suggest the existence of CD8 T cell-directed superantigenic activities associated with parasites.