Etanercept and infliximab are novel biological agents targeted against tumour necrosis factor alpha (TNFalpha), a key cytokine in the pathogenesis of rheumatoid arthritis (RA). We report the results of their use over a two year period in 94 patients with severe inflammatory arthritis. Eighty-eight adults with active inflammatory arthritis (82 with RA), unresponsive to all conventional treatment, received biological therapy in one of five specialist centres in Northern Ireland. 69 adult patients (78%) had a good response to treatment, four a partial response, and seven no response. The results of treatment could not be assessed in eight patients because they had only recently commenced therapy. Four patients had a mild allergic reaction to treatment but one patient developed fulminant lung fibrosis which may have been due to drug therapy and eventually proved fatal. There were four cases of major infection requiring hospitalisation. Two patients responded to treatment, but one succumbed to bacterial pneumonia, and another to bacterial meningitis. Six children with juvenile idiopathic arthritis (JIA) received etanercept. Four achieved a good response, one a partial response, and one no response to treatment. This study shows that the impressive response to anti-TNF therapies extends beyond the realm of clinical trials to everyday clinical practice. These agents represent a major advance in the treatment of severe inflammatory arthritis but they should be used with caution, particularly in the elderly and in patients who are predisposed to infection.