The authors carried out an open prospective study analyzing methotrexate (MTX) efficacy and toxicity in 34 patients with ankylosing spondylitis (AS) for a period of one year. All the patients presented with active axial disease, characterized by inflammatory spinal pain, prolonged morning stiffness, erythrocyte sedimentation rate (ESR) > or = 25 mm, and failure on treatment with non-steroidal anti-inflammatory drugs for a period of more than two years. MTX was taken at a single weekly intramuscular dose of 12.5 mg. Thirty-one patients (91%) concluded treatment. Eighteen patients (53%) were considered responders to MTX; most of them presented peripheral arthritis. Despite clinical improvement, axial measures were unaltered at the end of the study. The mean value of ESR decreased significantly at the end of the treatment (p=0.0001), predominantly in the responders group. Side effects were observed in 23 patients (68%) and included dyspeptic syndrome, transient elevation of liver enzymes, and dizziness. The results of this one year open study suggest that MTX can be an efficient drug in the treatment of AS.