Cytokincs are believed to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, for tumour necrosis factor alpha (TNF-α) both beneficial and deleterious effects have been reported. To obtain information about the involvement of this cytokine in the pathophysiology of SLE, serum levels of TNF-α, the soluble forms of the 55 and 75 IcDa tumour necrosis factor receptors (TNF-R55 and TNF-R75), and interleukin-6 (IL-6) were measured by ELISA in nine female patients over a period of 2 yr. Compared to healthy controls, levels of TNF-α (median 47pg/ml, range < 15-222 pg/ml), TNF-R55 (median 1.9ng/ml, range 0.8–10.8 ng/ml), TNF-R75 (median 4.7 ng/ml, range 1.5–15 ng/ml) and IL-6 (median 3.5 pg/ml, range < 3.5–52 pg/ml) were significantly elevated in SLE patients (P < 0.0001 vs controls in all cases). There were strong correlations between TNF-α and its soluble receptors (P < 0.0001). Moreover, TNF-α and both TNF-Rs strongly correlated with clinical and serological parameters of disease activity, such as the European Consensus Lupus Activity Measurement (ECLAM) score, anti-dsDNA antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anaemia (P < 0.0001 for all comparisons). TNF-α and TNF-R75 also correlated with IL-6 (P < 0.0001). However, no correlation between IL-6 and ECLAM was found, and the correlation of IL-6 with anti-dsDNA was relatively weak; in contrast, IL-6 correlated strongly with CRP and ESR (P < 0.0001). Although these data do not allow us ultimately to discriminate between beneficial and deleterious effects of TNF-α, they nevertheless suggest a central role for the TNF system in the pathophysiology of SLE.