Louvain rats were administered tumor necrosis factor alpha (TNF-alpha) via a continuous osmotic infusion pump. These rats were then immunized with native type II collagen (CII) to determine the effects of exogenous TNF-alpha on collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA). In this highly susceptible strain, 100% of experimental and control rats developed arthritis although TNF-alpha-treated rats had more severe disease as judged by both clinical and blinded radiographic parameters. Humoral responses to collagen were high in both groups, but cellular responses to CII were augmented by TNF-alpha. Serum IL-6 levels were significantly increased in all arthritic rats. This study suggests that TNF-alpha is a proinflammatory cytokine in CIA and that future studies targeting TNF-alpha might be therapeutic.