The influence of an active Trypanosoma ( Schizotrypanum) cruzi infection in mice and the subsequent immune response to an administered unrelated, erythrocyte antigen was studied. When mice were infected with blood forms of the parasite, a depression of the humoral immune response to injected burro erythrocytes (BE), was observed. The suppression became evident at a time when the magnitude of parasitemia and tissue forms was increasing in the sensitized and infected mice. The immunosuppressive effect induced by the infection to BE was demonstrated by a diminished direct (19S) and indirect (7S) antibody-forming cell response. Additionally, a significant increase in phagocytic activity was observed in T. cruzi-infected mice using colloidal carbon uptake experiments. Probable mechanisms of suppression are discussed and related to accepted lymphocyte activities.