Infection of a relatively resistant strain of mice (C57BL/6J) with the protozoan parasite Trypanosoma cruzi results in both the induction of parasite-specific T-helper cells and nonspecific suppressor cells. A time course study of the activation of help and suppression revealed that parasite-specific T-helper cell activity increases very early in infection (less than 12 days) at a time when suppression of non-parasite-specific responses and suppressor cell activity is increasing. Between 12 and 14 days of infection, the T-helper cell response to T. cruzi, as measured by the antibody response to hapten-T. cruzi in vitro, is suddenly and dramatically regulated. As reported previously, plastic and G-10 adherent cells appear to be responsible for the regulation of antibody responses to heterologous antigen during T. cruzi infection. These adherent suppressor cells are also responsible for the suppression of antibody responses to hapten-T. cruzi following the first 2 weeks of infection. Suppressor cells continue to regulate the parasite-specific response well into chronic infection even though the response to hapten-T. cruzi appears to return to normal levels. These results are the first to directly implicate nonspecific suppressor cells in the regulation of anti-T. cruzi humoral immune responses.