Chagas disease, caused by protozoan T. cruzi, affects ca. 13 million people in Latin America. Previous results showed that ~50% of infected outbred Syrian hamsters die or display acute phase symptoms (APS), such as cachexia and lethargy, 3 weeks post-infection (PI). This work evaluated cardiac parasitism, myocardial differential protein expression and cytokine expression in acutely T. cruzi infected hamsters with or without APS. Syrian hamsters (n=12) were infected i.p. with 105 Y-strain T. cruzi trypomastigotes and 6 animals were injected with saline solution. Myocardium left ventricles (LV) were collected 21 days PI. T. cruzi nests/antigen area in LV was analyzed by immunohistochemistry and morphometry. LV cytokine expression was analyzed by real-time RT-PCR. Differentially expressed LV proteins were identified by 2D-electrophoresis and peptide mass fingerprinting. Both the area of T. cruzi nest/antigen, and the expression of IFN-γ, TNF-α, and IL-10 were significantly increased in LV of animals with APS when compared to those without APS. Cytokine expression was significantly correlated with T. cruzi nest/antigen area. Energetic enzymes creatine kinase M and aconitase were down regulated in LV of animals with APS. The development of APS may be related to enhanced myocardial expression of cytokine genes associated to cardiac parasitism. Together, uncontrolled parasitism, inflammation and the possible deficit in energy metabolism may lead to the adverse outcomes of hamsters with APS. Supported by FAPESP/CNPq