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. Curr. Protoc. Immunol. 81:15.22.1‐15.22.12. © 2008 by John Wiley & Sons, Inc.