The objective was to evaluate tumour necrosis factor (TNF) status in patients with systemic juvenile chronic arthritis (s-JCA). Plasma levels of TNF-alpha, and serum levels of soluble TNF receptor 1 and 2 (sTNFR1 and sTNFR2) were measured using specific immunoassays in 20 patients with s-JCA, 10 with polyarticular JCA and 15 with pauciarticular JCA, and in 20 controls comparable for age. In patients with active s-JCA, circulating levels of TNF-alpha, sTNFR1 and sTNFR2 were significantly (P < 0.001) higher than those of controls. The levels of sTNFR1 and sTNFR2, but not those of TNF-alpha, were associated with the persistence and severity of systemic symptoms and were significantly correlated with prolongation of partial thromboplastin time and decrease in prothrombin activity. In two patients evaluated during a s-JCA-associated macrophage activation syndrome, a marked increase in sTNFR1 and sTNFR2 was found. Our results suggest that in s-JCA, TNF is involved in systemic manifestations, in the subclinical coagulation abnormalities, and in the development of the macrophage activation syndrome.