This article examines some fundamental features of the histopathology of ankylosing spondylitis (AS) such as inflammation in the entheses and syndesmophyte formation. This may be linked to the generation of transforming growth factor in inflammation, which can stimulate bone formation, and to the molecular composition of entheses where molecules are present, such as the proteoglycan aggrecan, that are normally found in cartilage. Immunity to these molecules is observed in patients with AS and in experimental immunity to aggrecan, or the G1 domain only, which can cause spondylitis. Involvement of other tissues (the eye and arterial vessels) may be due to crossreactive immunity.