Infection of mice with Trypanosoma cruzi results in a severe immunosuppression, accompanied by the appearance of autoimmune symptoms. We have previously shown that proliferation and interleukin 2 production by concanavalin A-stimulated T cells from infected mice is severely depressed. In this study we show that at least two phenomena are responsible for this depression. First, mixing experiments showed the existence, in spleens of infected animals, of adherent, Thy-1-negative and radioresistant suppressor cells. Second, studies of enriched T cell populations and analysis of precursors by limiting dilution showed that the T cell compartment itself was impaired in infected animals: responses of enriched T cells, even when reconstituted with normal accessory cells, reached only 40% of those obtained with normal uninfected mice.