Previous studies have shown that circulating levels of cytokines are increased in patients with congestive heart failure (CHF), resulting in myocardial depression. In this work, we have determined serum levels of TNF-α and IFN-γ by ELISA, detected sTNFR-I by dot ELISA, as well as TNFα, IL-6, IL-10 and granulysin mRNA in unstimulated peripheral blood mononuclear cells (PBMC) by RT-PCR in CHF patients. Such patients were classified using New York Heart Association criteria and compared to a control group of volunteers without CHF. The performed echocardiographic evaluations showed a significant difference between the control group and the patients. Additionally, the ejection fraction and the left ventricular fractional shortening showed a direct relation with functional classes, varying in inverse proportion. Generally, the studied cytokines in serum or PBMC did not correlate either to functional classes or to the presence/absence of CHF. However, the granulysin mRNA was detected in most of the patients tested as compared to controls. Moreover, the qualitative detection of the sTNFR-I also made it possible to discriminate between patients and the control group. Functional classes could be separated because of a direct association between CHF severity and elevated levels of sTNFR-I, defined by intensity of signal in dot-ELISA. Our results suggest that detection of granulysin mRNA as well as the detection of sTNFR-I appear to have a clinical relevance as markers of immune activation in CHF.