OBJECTIVE: Mosquito-borne alphaviruses such as chikungunya virus, O'nyong-nyong virus and Ross River virus (RRV) cause sporadic, sometimes large, outbreaks of rheumatic disease worldwide. Here we test the effect of treating RRV-induced arthritis using the anti-TNF drug, etanercept, in a mouse model of rheumatic disease. METHODS: Mice were infected with RRV and treated with etanercept. Weight loss, tissue viral titers and histological examination of muscle and joint tissues were undertaken. RESULTS: RRV-infected mice treated with etanercept showed increased weight loss, higher viral titres in muscle, joints and blood, more tissue damage and inflammatory cell recruitment than RRV-infected mice without treatment. CONCLUSION: Anti-TNF therapy is unlikely to have utility in treating alphaviral arthritides. During alphaviral epidemics careful monitoring of patients being treated with anti-TNF drugs may be warranted.