Inflammatory cells positive for the cytokines IL-2, IL-4, IL-6, TNF-alpha, and IFN-gamma and for IL-2R, as well as CD8+ and CD4+ T cells and B cells were quantified using an immunoperoxidase technique in 25 fresh myocardial fragments from patients presenting with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi antigens (Ags) in the myocardium was also investigated. The cases were grouped into group A (no Ag), group B (scarce extramyocardial fiber Ags), and group C (intramyocardial pseudocysts and extramyocardial fiber Ags). IL-2 was detected in very few cells (0.30 +/- 0.40 positive cells/hpf), suggesting immunological imbalance in chronic chagasic patients. IFN-gamma+ was the cytokine most frequently demonstrated (7.52 +/- 5.87 positive cells/hpf) and there was a good correlation between the number of IFN-gamma+ cells and CD8+ T cells in group A. IL-4+ cells were present in higher numbers in group C (2.78 +/- 1.49 positive cells/hpf). TNF-alpha+ (1.59 +/- 1.68 positive cells/hpf) and IL-6+ (2.76 +/- 2.32 positive cells/hpf) cells were present in moderate numbers. Fewer B cells were present, not related with the intensity of T. cruzi Ags. These results suggest that cytokines, as they occur in other infectious diseases, play a fundamental role in the control of T. cruzi in chronic human chagasic disease. A fatal outcome seems to be associated with the increased production of cytokines derived from the Th2 subpopulation of the CD4+ T cells.