The responses of spleen cells from mice infected with Trypanosoma cruzi to T and B cell-specific mitogens were monitored during the acute and chronic stages of the infection. Responses to either T (phytohemagglutinin or concanavalin A) or B (endotoxic lipopolysaccharide) cell mitogens measured on days 5, 10, 15, and 20 postinfection, i.e., at different times during the acute period, were markedly reduced. Responses measured on days 54 and 90, i.e., during the chronic stage, did not differ significantly from those of normal mouse spleen cells. Proportions of T and B lymphocytes in the spleen were reduced and unaltered, respectively, during acute T. cruzi infection but were comparable to normal values during the chronic state. These results highlight a return of normal T and B lymphocyte responses during chronic experimental Chagas' disease and suggest that transition from the acute to the chronic phase of the infection may be immunologically regulated.