Interleukin 1 (IL-1) is a polypeptide released by activated macrophages and is thought to be a key mediator of host responses to infection and inflammation. The availability of highly purified and recombinant material has now permitted the evaluation of IL-1 as a mediator of chronic inflammatory processes in vivo. We have demonstrated that intraarticular injection of IL-1 into rabbit knee joints induces the accumulation of polymorphonuclear and mononuclear leukocytes in the joint space and the loss of proteoglycan from the articular cartilage. The effects on cartilage could not be explained solely by the presence of leukocytes, since injections of endotoxin also stimulated leukocyte accumulation in the joint but had no effect on proteoglycan loss. Responses to IL-1 were not associated with increased production of the icosanoids prostaglandin E2 or leukotriene B4 and were not reduced by an inhibitor of their synthesis. The pattern of leukocyte infiltration and cartilage breakdown 24 hr after IL-1 injection was similar to that seen in animals with antigen-induced arthritis of 1 week's duration. These observations support the hypothesis that IL-1 acts directly to mediate the erosive processes of chronic arthritis.