We describe a 37-yr-old Caucasian male suffering from ankylosing spondylitis (AS) with long-standing severe inflammatory lumbar pain and hip arthritis who was refractory to non-steroidal anti-inflammatory drugs, sulphasalazine and methotrexate up to 25 mg/week. In this patient, administration of an i.v. loading dose of azathioprine (AZA; 40 mg/kg for 36 h followed by 2 mg/kg oral AZA therapy) induced a dramatic response in his clinical condition. Indeed, objective and subjective clinical variables improved within 1 week and were corroborated by a decline in the levels of the inflammatory parameters; anaemia was reported at month 3 but was rapidly reversible. If confirmed, an i.v. loading dose of AZA could represent a valuable alternative in severe and refractory AS, but toxicity of this regimen should be carefully analysed.