Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA). To investigate the role of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in arthritic processes we studied the effect of neutralizing antibodies against murine IL-1 and TNF in murine collagen-induced arthritis (CIA). Combined i.p. injection of anti-IL-1 and anti-IL-1 (anti-IL-1,), given before onset of the disease, completely prevented CIA. In contrast, treatment with anti-TNF at this time point only delayed the onset of arthritis. Remarkably, a single injection of anti-IL-1, was also highly effective in suppressing established arthritis, reducing both inflammation and cartilage destruction. Suppression was most pronounced with the combination of anti-IL-1 and , but anti-IL-1 alone also gave significant relief. Specific antibodies against TNF had no effect on established CIA. Of interest, anti-IL-1, treatment started after onset of CIA completely normalized chondrocyte synthetic function, which was highly suppressed in the non-treated group. It is concluded that IL-1 and TNF are important cytokines during the onset of CIA and that IL-1 is the key mediator of inflammation and cartilage damage in established CIA.