Tumor Necrosis Factor alpha is an important mediator of immunity and inflammation, and because of its biologic activities (activation of neutrophils, release of arachidonic acid metabolites from synovial cells, induction of cartilage resorption and inhibition of proteoglycan release in cartilage) is one of the potential mediators of the chronic inflammation in rheumatoid arthritis. A commercially available ELISA was used to evaluate serum levels of Tumor Necrosis Factor alpha (TNF alpha) in patients with rheumatic diseases. We tested sera from patients with rheumatoid arthritis, seronegative arthritis, osteoarthritis, post-traumatic arthritis, systemic lupus erythematosus, progressive systemic sclerosis and normal healthy subjects as controls. Furthermore, we statistically analysed data to investigate whether a correlation exists between serum levels of TNF alpha and some humoral indexes of disease activity. The results show strikingly higher TNF alpha levels in Rheumatoid Arthritis patients when compared both to normal controls and arthritis or connective tissue disease controls. TNF alpha was also found to correlate positively with levels of the rheumatoid factor as measured either by means of the latex agglutination test (LAT) or by nephelometry. These results support the suggestion that TNF alpha plays a central role in the pathogenesis of rheumatoid arthritis.