BACKGROUND TNFalpha, a proinflammatory cytokine expressed under several conditions in the myocardium, may contribute to myocardial damage in heart failure (HF). The aim of the study was to determine TNFalpha concentrations and their relation to severity, mortality, and clinical, biochemical and echocardiographic parameters in patients with stable chronic heart failure. METHODS In a prospective study in 128 patients with HF, average follow-up 33 mos, serum concenrations of TNFalpha were determined, and clinical, biochemical and echocardiographic characteristics and mortality were recorded. Serum TNFalpha concentrations were also determined in 35 healthy subjects. Univariate and multivariate analyses were performed to determine variables that could influence TNFalpha concentrations, and that could predict mortality. RESULTS Patients with HF have higher serum concentrations of TNFalpha than controls (6.72+/-0.2 vs 5.5+/-0.2 pg/ml, P=0.02). Patients with functional class I had lower concenrations of TNFalpha than patients with functional classes II and III (P=0.05 and P=0.001, respectively). Variables associated with higher concentrations of TNFalpha were; lower ejection fraction (P=0.04), worse functional class (P=0.007), coronary artery disease (P=0.05), chronic renal failure (P=0.02), arterial hypertension (P=0.05), higher concentrations of epinephrine (P=0.03) and norepinephrine (P=0.05). On follow-up, factors associated with decline in ejection fraction were arterial hypertension and higher total catecholamines. Factors associated with higher mortality were hypertension, elevated concentrations of TNFalpha and troponin T. Endothelin levels correlated with worsening functional class. CONCLUSIONS Serum TNFalpha and troponin T concentrations are independent predictors of severity and mortality in stable HF patients.