Interleukin-6 (IL-6) is a monokine with a number of biological activities, which are intimately related to inflammatory responses. We have measured IL-6 levels in synovial fluid (SF) and serum (Se) of patients with rheumatic diseases. SF-IL-6 levels were a thousand-fold higher than corresponding Se levels and a positive correlation was found between SF and Se levels suggesting that Se-IL-6 is derived from IL-6 produced in the joint. Se levels of IL-6 were also positively correlated to C-reactive protein (CRP) levels, supporting the in vitro experiments showing that IL-6 stimulates hepatocytes to produce CRP. Finally we observed a positive correlation between SF-IL-6 levels and the local activity score.