BACKGROUND In randomised trials, treatment with anti-tumour necrosis factor alpha drugs has been shown to be efficacious for patients with rheumatoid arthritis. We analysed the effectiveness and toxicity of etanercept treatment in our day-to-day rheumatology practice at the University Hospital of Northern Norway. METHODS Patients with active polyarthritis who had failed at least three different disease-modifying anti-rheumatic drugs including methotrexate and/or combination therapy were consecutively included in an open study when they started etanercept therapy (25 mg twice per week subcutaneously). During follow up we noted the number of swollen and tender joints, took visual analogue scores (0-100 millimetre) for pain and global well-being, administered the Modified Health Assessment Questionnaire, performed laboratory tests, and took note of side effects. RESULTS Between April 1999 and July 2001, etanercept treatment was initiated in 71 patients. An ACR-20 response (20% improvement according to American College of Radiology criteria) occurred in 57% of patients after one month of treatment and in 70 % after three months, ACR-50 response in 24% and 42%, and ACR-70 response in 6% and 20%. While half of all patients reported side effects, only five patients (7%) discontinued treatment because of them. CONCLUSIONS Etanercept is effective therapy for many patients with severe chronic polyarthritis in clinical practice. Short-term side effects occur more frequently than reported and seem less frequent with concomitant methotrexate therapy. Long-term side effects are still unknown and require close monitoring.