Based upon the clinical presentation of chronic fatigue syndrome (CFS), we hypothesized that proinflammatory cytokines may play a role in the pathogenesis of the disease. We therefore undertook a retrospective cross-sectional study to examine the role of TNF- in patients with CFS. Our results suggest a significant increase serum TNF- in patients with CFS (P < 0.0001) compared to non-cfs controls. this study supports the further examination of the role of proinflammatory mediators in cfs. furthermore, the clinical testing of> blockers and other anti-inflammatory agents for the treatment of this disease is warranted.