Ankylosing enthesopathy is a spontaneously occurring progressive stiffening of the ankle and/or tarsal joints in mice of C57Black background. In C57BL/10 mice and mice of the same genetic background that had been made transgenic for HLA-B27, the start of the disease was detected by weekly testing for decreased mobility in the ankle/tarsus region. Ankylosing enthesopathy was found to begin with a short phase of proliferative inflammation of the joints and adjacent tissues, with some fibrinous exsudation, some leucocytic infiltration and slight bone erosion. This inflammation is soon accompanied and followed by proliferation of cartilaginous cells at the bone insertions of joint capsule ligaments (entheses). Ossification of the cartilage proliferations and some desmal ossification lead to large osteophytes that inhibit mobility. Fusion of osteophytes occasionally leads to marginal ankylosis. The histopathology of the successive stages of murine ankylosing enthesopathy and the preponderance in males and HLA-B27 transgenic mice are reminiscent of ankylosing spondylitis in man. The spine, however, was not affected.