To investigate the possible role of IL-6 in the activation of the autoimmune process in systemic lupus erythematosus (SLE), we serially measured concentrations of IL-6, IgG, and anti-dsDNA antibodies before and during exacerbations in patients with SLE. In addition, we serially related the IL-6 response to the generation of the acute phase reactant C-reactive protein (CRP). Sixteen consecutive patients who developed an exacerbation were analysed in this study. Blood samples were drawn in EDTA monthly. At the time of maximal disease activity during exacerbation, IL-6 plasma concentrations were increased (greater than or equal to 6 pg/ml) in 12 out of the 16 cases. Concentrations of IL-6 correlated with the concentrations of CRP (P less than 0.01) and the score of the disease activity index (P less than 0.05). No correlation was found between IL-6 concentrations and concentrations of anti-dsDNA or IgG. The course of changes in IL-6 concentrations before the exacerbation was variable. Five out of the 16 exacerbations studied were characterized by a prominent rise of IL-6 at the time of maximum disease activity. In this subgroup serositis as well as elevated concentrations of CRP were observed more frequently (P less than 0.02). Seven exacerbations were not accompanied or preceded by changes in IL-6 concentrations and showed generally low IL-6 concentrations. In this latter subgroup cerebral involvement was seen more frequently (P less than 0.02). Our data do not suggest a pathogenic role for IL-6 in the generation of IgG and/or anti-dsDNA antibodies before exacerbations. Rises of IL-6 concentrations before exacerbations in SLE seem only to occur in a subgroup of patients with SLE characterized by the presence of serositis and elevated concentrations of CRP during exacerbation.