There have been few well-conducted studies into the efficacy of methotrexate in Ankylosing spondylitis. The results of a new prospective study in 51 patients are presented in this issue but the clinical response was poor. A recurring theme, however, is the promising effect noted on peripheral joints compared with that on the axial skeleton. Recent histological and magnetic resonance imaging evidence suggests that synovitis and subchondral bone marrow changes offer a more rational explanation for widespread joint destruction than does enthesitis alone. Furthermore, enthesis lesions close to synovial joints occur frequently and may be intimately linked with peripheral joint synovitis. At the moment there is no hard evidence of efficacy in axial disease, but these observations raise the possibility that suppression of synovitis might help in the spine, and that enthesitis might respond wherever it is anatomically. Thus further long-term, placebo-controlled studies are needed to address specifically the issues of enthesitis. spinal symptom relief and the suppression of long-term ankylosis.