Infection of several mouse strains with Trypanosoma cruzi stimulates high levels of T and B lymphocyte activities which persist during the chronic phase and is followed by specific immunosuppression and severe aftoimmune pathology. Infected BALB. Xid mice carrying an X-llnked mutation and lacking CD5 B cells, display poor B cell responses toT. Cruzi infection, accompanied by low levels of specific and non-specific immunoglobulins in the serum. However, these animals control parasitemia, do not show the wasting observed in BALB/c mice, and develop almost no pathology early in the chronic phase. The infection of (BALB. Xid female x BALB/c male) F1 animals shows that immunodefective males behave like Xid animals in contrast to females which respond as normal BALB/C mice. These results indicate that the Xld locus controls lymphocyte responses, parasite clearance and pathology in experimental Charges' disease.