C3H/He and C57B1/6 mice were inoculated with 500 Trypanosoma cruzi trypomastigotes (Strain Y). During the acute phase infected mice presented parasitemia and enlargement of lymph nodes and spleens and intracellular parasites were observed in the heart. Examinations of cells derived from spleen and lymph nodes showed increased numbers of IgM and IgG-bearing cells. During the peak of splenomegaly, about day 17 post-infections, splenic lymphocytes showed a marked decrease in responsiveness to T and B-cell mitogens, parasite antigens and plaque forming cells (PFC) to sheep red blood cells (SRBC). Unfractionated or plastic adherent splenic cells from mice, obtained during the acute phase were able to suppress the response to mitogens by lymphocytes from uninfected mice. During the chronic phase. Disappearance of parasitemia and intracellular parasites in the hearts as well as a decrease in spleen size, was observed. These changes preceded the complete recovery of responsiveness to mitogens and T. cruzi antigens by C57B1/6 splenic lymphocytes. However, this recovery was only partial in the C3H/He mice, known to be more sensitive to T. cruzi infection. Partial recovery of humoral immune response also occurred in both strains of mice during the chronic phase.