To attempt to clarify the role of u-PA in arthritis progression, we have modified one of the systemic models - namely the K/BxN serum transfer model - by incorporating an i.a. injection of saline to induce some trauma into a knee joint or, in other words, to combine aspects of the systemic and monoarticular models in u-PA-/- mice; a similar approach by Li and colleagues [21] showed that the joint trauma caused by a local i.a. injection of type II collagen into CIA-immunized plasminogen-/- mice, which are normally resistant to arthritis development [5], led to arthritis in the injected joint. This evidence concerns the gene PLG and arthritic joint disease.