An imbalance of TNF system activity has been reported in patients with myotonic dystrophy type 1 (DM1). Nevertheless, the question whether TNF-alpha action is directly implicated in the pathogenesis of DM1 or is a simple marker of disease activity is still open. Therefore, the present study was aimed to investigate serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in association with the disease stage, cytosine-thymine-guanine (CTG) expansion and cardiac function of 56 patients with DM1 (40+/-14 years) and 28 healthy controls (42+/-12 years). All subjects were submitted to resting electrocardiogram (EKG), Signal-averaged EKG (SA-EKG), and M-mode/2-D echocardiography. TNF-alpha levels were higher in patients compared to controls (p<0.0003) and were associated to disease stage (p<0.02). Significant correlation were observed between TNF and CTG expansion (p<0.005) or PQ intervals (p<0.0005). Ventricular late potentials (VLPs) occurred in 54% of cases. In these patients, TNF-alpha levels were higher compared to those without VLPs (p<0.05). We may conclude that TNF-alpha levels might represent and adjunctive criterion for disease staging in patients with myotonic dystrophy type 1, and that elevated TNF levels in DM1 may lead to cardiac fibrosis affecting diastolic function, conduction, and automaticity.