OBJECTIVE To evaluate safety and clinical response to treatment with etanercept in the polyarticular course of patients with juvenile rheumatoid arthritis (JRA). METHODS Ten patients were studied (8 female, 2 male; 6 polyarticular JRA, 4 systemic onset; mean age 13.3 yrs; mean duration of disease 6.6 yrs). Patients received 0.4 mg/kg etanercept subcutaneously twice weekly in addition to their existing therapeutic regimen. Observed duration of treatment ranged between 4 and 12 months. RESULTS Patients tolerated treatment with etanercept well. No serious adverse events were noted. Treatment response showed considerable improvement of morning stiffness (mean reduction of 96 min approximately equal to -93%) and joint counts including swollen joints (delta -8.2 approximately equal to -40%), tender joints (delta -9.2 approximately equal to -88%), and total joints (delta -9.8 approximately equal to -37%). Laboratory results included decreases in ESR (delta -46 mm/h approximately equal to -53%) and improvement of anemia. CONCLUSIONS Our results confirm etanercept is a powerful adjunct in the therapy of polyarticular JRA resistant to conventional treatment regimens.