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We measured interleukin‐6 (IL‐6) levels in 70 serum samples obtained from 25 patients with systemic‐onset juvenile rheumatoid arthritis (JRA), using the hybridoma cell line B9. Patients with systemic‐onset JRA had significantly elevated serum IL‐6 levels during active disease (mean ± SD 92.1 ± 75.1 hybridoma growth factor units/ml; P < 0.00001 versus healthy age‐matched controls), but not during remission. Serum IL‐6 levels correlated with the extent and severity of joint involvement (P < 0.001) and with platelet counts (P < 0.05). Our data suggest that IL‐6 plays a significant role in the pathogenesis of systemic‐onset JRA.