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Autologous mixed lymphocyte reactions (AMLR) were studied in 18 individuals chronically infected with Trypanosoma cruzi. These individuals were further classified into three clinical groups: the asymptomatic indeterminate form (n = 5); the mega disease form (n = 5); and the cardiomyopathy form (n = 8). While patients with mega disease showed a normal proliferative response when compared with normal controls, the indeterminate group showed a lowered response in sharp contrast with the heart disease group, which presented a very high proliferative response to autologous non-T cells. These abnormal AMLR represent direct evidence for an immunoregulatory malfunction which may be involved in the inflammatory cardiac damage in chronic Chagas' disease.