Pro-inflammatory cytoldnes such as tumour necrosis factor alpha (TNFα) have been implicated in the pathogenesis of rheumatoid arthritis (RA), and have therefore become therapeutic targets. An engineered human antibody, CDP571, that neutralizes human TNFα was administered intravenously in single doses of 0.1, 1.0 or 10mg/kg to patients with active RA (n = 24). The effects of the antibody were compared in a double-blind fashion with thoseof placebo (n = 12). In an open continuation phase patients were given either 1.0 or 10 mg/kg. We found that CDP571 was well tolerated and caused reductions in markers of disease activity such as erythrocyte sedimentation rate (ESR) and serum C-reactivc protein (CRP): this was confirmed by a reduction in the disease activity score (DAS). There was a reduction in the number of tender joints, maximal in degree and duration after 10 mg/kg. Patients also documented a reduction of pain and relief of arthritis symptoms. The effects of 10 mg/kg CDP571 on ESR, CRP, tender joints, pain and symptom relief compared to placebo were statistically significant at weeks 1 or 2. The continuationphase, although open, confirmed both the safety and the beneficial effects of CDP571 in active RA. In conclusion CDP571, an engineered human anti-TNFα antibody, is well tolerated and, after a single dose of 10 mg/kg, provides improvements in symptoms, signs and serological markers of disease activity in patients with active RA.