Lymphocyte blastogenic response to various parasite-specific and non-parasite antigens was measured in 31 Trypanosoma cruzi-infected individuals representing the indeterminate, megadisease and cardiomyopathy forms of Chagas' disease. The non-parasite antigens and mitogens stimulated responses in the peripheral blood mononuclear cell (PBMC) cultures of the infected individuals to levels not different than the stimulation seen in PBMC of the normal control group (n = 10). The cell culture antigen (CC-Ag) derived from trypomastigote-amastigote forms of T. cruzi and the epimastigote antigen (EPI-Ag) elicited a strong response among all infected individuals in contrast to virtually no response among the normal controls. Comparisons among the individuals with T. cruzi infection stimulated with EPI-Ag showed no significant difference between the clinical groups. However, stimulus with CC-Ag showed the megadisease group response to be greater than the response of the indeterminate group, but not different than than of the cardiomyopathy group. The possible biological implications of these findings are discussed.