['To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1beta and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA).', 'Twenty-two patients with systemic-onset JIA were treated with the IL-1 receptor antagonist (IL-1Ra) anakinra. Monocytes from 18 patients and 20 healthy donors were activated by different Toll-like receptor ligands. Intracellular and secreted IL-1beta and IL-18 were analyzed by Western blotting and enzyme-linked immunosorbent assay.', 'Ten patients with systemic-onset JIA exhibited a dramatic response to anakinra and were classified as complete responders. Eleven patients had an incomplete response or no response, and 1 patient could not be classified in terms of response. Compared with patients who had an incomplete response or no response, complete responders had a lower number of active joints (P = 0.02) and an increased absolute neutrophil count (P = 0.02). In vitro IL-1beta and IL-18 secretion in response to various stimuli was not increased and was independent of treatment efficacy. Likewise, secretion of IL-1Ra by monocytes from patients with systemic-onset JIA was not impaired. An overall low level of IL-1beta secretion upon exposure to exogenous ATP was observed, unrelated to treatment responsiveness or disease activity.'] Does the pattern of response to anti-interleukin-1 treatment distinguish two subsets of patients with systemic-onset juvenile idiopathic arthritis?