A model system has been described in which a single injection of Ovalbumin into the knee joints of previously sensitized rabbits consistently produced a chronic, self-perpetuating reaction which was grossly and histologically similar to human rheumatoid arthritis. This reaction was markedly diminished in knees receiving intra-articular 5-fluorouracil three times a week. The drug itself produced no demonstrable injury to the normal joint and was well tolerated systemically in reasonable doses. These observations raise the question whether this agent might serve some clinical role as an adjunct in the management of human rheumatoid arthritis. Further animal experimentation must be carried out to establish the mechanism of action and optimum treatment regimen.