Mice expressing both the T cell receptor (TCR) transgene KRN and the MHC class II molecule A(g7) (K/BxN mice) develop severe inflammatory arthritis, and serum from these mice causes a similar arthritis in a wide range of mouse strains, due to autoantibodies recognizing glucose-6-phosphate isomerase (GPI). K/BxN transgenic mice have been useful for investigating the development of autoimmunity, and the serum transfer model has been particularly valuable in eliciting mechanisms by which anti-GPI autoantibodies induce joint-specific inflammation. This unit describes detailed methods for the maintenance of a K/BxN colony, induction of arthritis by serum transfer, clinical evaluation of arthritis, and measurement of anti-GPI antibodies. Copyright 2008 by John Wiley & Sons, Inc.